start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=1 article-no= start-page=4 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250114 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Differentially Expressed Nedd4-binding Protein Ndfip1 Protects Neurons Against Methamphetamine-induced Neurotoxicity en-subtitle= kn-subtitle= en-abstract= kn-abstract=To identify factors involved in methamphetamine (METH) neurotoxicity, we comprehensively searched for genes which were differentially expressed in mouse striatum after METH administration using differential display (DD) reverse transcription-PCR method and sequent single-strand conformation polymorphism analysis, and found two DD cDNA fragments later identified as mRNA of Nedd4 (neural precursor cell expressed developmentally downregulated 4) WW domain-binding protein 5 (N4WBP5), later named Nedd4 family-interacting protein 1 (Ndfip1). It is an adaptor protein for the binding between Nedd4 of ubiquitin ligase (E3) and target substrate protein for ubiquitination. Northern blot analysis confirmed drastic increases in Ndfip1 mRNA in the striatum after METH injections, and in situ hybridization histochemistry showed that the mRNA expression was increased in the hippocampus and cerebellum at 2 h-2 days, in the cerebral cortex and striatum at 18 h-2 days after single METH administration. The knockdown of Ndfip1 expression with Ndfip1 siRNA significantly aggravated METH-induced neurotoxicity in the cultured monoaminergic neuronal cells. These results suggest that drastic increases in Ndfip1 mRNA is compensatory reaction to protect neurons against METH-induced neurotoxicity. en-copyright= kn-copyright= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=CadetJean Lud en-aut-sei=Cadet en-aut-mei=Jean Lud kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Molecular Neuropsychiatry Section, Intramural Research Program, NIH/ NIDA kn-affil= en-keyword=Methamphetamine kn-keyword=Methamphetamine en-keyword=Neurotoxicity kn-keyword=Neurotoxicity en-keyword=Nedd4 kn-keyword=Nedd4 en-keyword=Ndfip1 kn-keyword=Ndfip1 en-keyword=Differential display kn-keyword=Differential display END start-ver=1.4 cd-journal=joma no-vol=38 cd-vols= no-issue=2 article-no= start-page=394 end-page=408 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200221 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The neurotoxicity of psychoactive phenethylamines “2C series” in cultured monoaminergic neuronal cell lines en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose The aim of this study was to evaluate the neurotoxicity of psychoactive abused 2,5-dimethoxy-substituted phenethylamines “2C series” in monoaminergic neurons.
Methods After the exposure to “2C series”, 2,5-dimethoxy-4-propylthiophenethylamine (2C-T-7), 2,5-dimethoxy-4-isopropylthiophenethylamine (2C-T-4), 2,5-dimethoxy-4-ethylthiophenthylamine (2C-T-2), 2,5-dimethoxy-4-iodophenethylamine (2C-I) or 2,5-dimethoxy-4-chlorophenethylamine (2C-C), we examined their neurotoxicity, morphological changes, and effects of concomitant exposure to 3,4-methylenedioxymethamphetamine (MDMA) or methamphetamine (METH), using cultured neuronal dopaminergic CATH.a cells and serotonin-containing B65 cells.
Results Single dose exposure to “2C series” for 24 h showed significant cytotoxicity as increase in lactate dehydrogenase (LDH) release from both monoaminergic neurons: 2C-T-7, 2C-C (EC50; 100 ?M)?>?2C-T-2 (150 ?M), 2C-T-4 (200 ?M)?>?2C-I (250 ?M) in CATH.a cells and 2C-T-7, 2C-I (150 ?M)?>?2C-T-2 (250 ?M)?>?2C-C, 2C-T-4 (300 ?M) in B65 cells. The “2C series”-induced neurotoxicity in both cells was higher than that of MDMA or METH (EC50:???1?2 mM). In addition, apoptotic morphological changes were observed at relatively lower concentrations of “2C series”. The concomitant exposure to non-toxic dose of MDMA or METH synergistically enhanced 2C series drugs-induced LDH release and apoptotic changes in B65 cells, but to a lesser extent in CATH.a cells. In addition, the lower dose of 2C-T-7, 2C-T-2 or 2C-I promoted reactive oxygen species production in the mitochondria of B65 cells, even at the early stages (3 h) without apparent morphological changes.
Conclusion The 2,5-dimethoxy-substitution of “2C series” induced severe neurotoxicity in both dopaminergic and serotonin-containing neurons. The non-toxic dose of MDMA or METH synergistically enhanced its neurotoxicity in serotonergic neurons. en-copyright= kn-copyright= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FunadaMasahiko en-aut-sei=Funada en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Division of Drug Dependence, National Institute of Mental Health, National Center of Neurology and Psychiatry kn-affil= en-keyword=Psychoactive drugs kn-keyword=Psychoactive drugs en-keyword=2,5-Dimethoxy-substituted phenethylamines kn-keyword=2,5-Dimethoxy-substituted phenethylamines en-keyword=Neurotoxicity kn-keyword=Neurotoxicity en-keyword=Serotonin-containing neurons kn-keyword=Serotonin-containing neurons en-keyword=Dopamine neurons kn-keyword=Dopamine neurons en-keyword=Reactive oxygen species kn-keyword=Reactive oxygen species END start-ver=1.4 cd-journal=joma no-vol=820 cd-vols= no-issue= article-no= start-page=137598 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neurogenesis impairment with glial activation in the hippocampus-connected regions of intracerebroventricular streptozotocin-injected mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Adult neurogenesis in the hippocampus and subventricular zone (SVZ) is impaired by intracerebroventricular administration of streptozotocin (icv-STZ) to rodents. Although neural cells in the several brain regions which connect with the hippocampus or SVZ is thought to be involved in the adult neurogenesis, few studies have investigated morphological alterations of glial cells in these areas. The present study revealed that icv-STZ induces reduction of neural progenitor cells and a dramatic increase in reactive astrocytes and microglia especially in the hippocampus and various hippocampus-connected brain areas. In contrast, there was no significant neuronal damage excluding demyelination of the stria medullaris. The results indicate the hippocampal neurogenesis impairment of this model might be occurred by activated glial cells in the hippocampus, or hippocampus-connected regions. en-copyright= kn-copyright= en-aut-name=MasaiKaori en-aut-sei=Masai en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakayamaYuta en-aut-sei=Nakayama en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShinKotaro en-aut-sei=Shin en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SugaharaChiaki en-aut-sei=Sugahara en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YasuharaTakao en-aut-sei=Yasuhara en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Medical School kn-affil= affil-num=3 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Streptozotocin kn-keyword=Streptozotocin en-keyword=Adult neurogenesis kn-keyword=Adult neurogenesis en-keyword=Astrocyte kn-keyword=Astrocyte en-keyword=Microglia kn-keyword=Microglia END start-ver=1.4 cd-journal=joma no-vol=174 cd-vols= no-issue=6 article-no= start-page=533 end-page=548 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230919 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Phosphorylated SARM1 is involved in the pathological process of rotenone-induced neurodegeneration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sterile alpha and Toll/interleukin receptor motif-containing protein 1 (SARM1) is a NAD+ hydrolase that plays a key role in axonal degeneration and neuronal cell death. We reported that c-Jun N-terminal kinase (JNK) activates SARM1 through phosphorylation at Ser-548. The importance of SARM1 phosphorylation in the pathological process of Parkinson’s disease (PD) has not been determined. We thus conducted the present study by using rotenone (an inducer of PD-like pathology) and neurons derived from induced pluripotent stem cells (iPSCs) from healthy donors and a patient with familial PD PARK2 (FPD2). The results showed that compared to the healthy neurons, FPD2 neurons were more vulnerable to rotenone-induced stress and had higher levels of SARM1 phosphorylation. Similar cellular events were obtained when we used PARK2-knockdown neurons derived from healthy donor iPSCs. These events in both types of PD-model neurons were suppressed in neurons treated with JNK inhibitors, Ca2+-signal inhibitors, or by a SARM1-knockdown procedure. The degenerative events were enhanced in neurons overexpressing wild-type SARM1 and conversely suppressed in neurons overexpressing the SARM1-S548A mutant. We also detected elevated SARM1 phosphorylation in the midbrain of PD-model mice. The results indicate that phosphorylated SARM1 plays an important role in the pathological process of rotenone-induced neurodegeneration. en-copyright= kn-copyright= en-aut-name=MurataHitoshi en-aut-sei=Murata en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PhooMay Tha Zin en-aut-sei=Phoo en-aut-mei=May Tha Zin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OchiToshiki en-aut-sei=Ochi en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoKen-ichi en-aut-sei=Yamamoto en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KinoshitaRie en-aut-sei=Kinoshita en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=JNK kn-keyword=JNK en-keyword=PARK2 kn-keyword=PARK2 en-keyword=Parkinson’sdisease kn-keyword=Parkinson’sdisease en-keyword=Phosphorylation kn-keyword=Phosphorylation en-keyword=SARM1 kn-keyword=SARM1 END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=16 article-no= start-page=8689 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210813 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Glutathione and Related Molecules in Parkinsonism en-subtitle= kn-subtitle= en-abstract= kn-abstract=Glutathione (GSH) is the most abundant intrinsic antioxidant in the central nervous system, and its substrate cysteine readily becomes the oxidized dimeric cystine. Since neurons lack a cystine transport system, neuronal GSH synthesis depends on cystine uptake via the cystine/glutamate exchange transporter (xCT), GSH synthesis, and release in/from surrounding astrocytes. Transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), a detoxifying master transcription factor, is expressed mainly in astrocytes and activates the gene expression of various phase II drug-metabolizing enzymes or antioxidants including GSH-related molecules and metallothionein by binding to the antioxidant response element (ARE) of these genes. Accumulating evidence has shown the involvement of dysfunction of antioxidative molecules including GSH and its related molecules in the pathogenesis of Parkinson's disease (PD) or parkinsonian models. Furthermore, we found several agents targeting GSH synthesis in the astrocytes that protect nigrostriatal dopaminergic neuronal loss in PD models. In this article, the neuroprotective effects of supplementation and enhancement of GSH and its related molecules in PD pathology are reviewed, along with introducing new experimental findings, especially targeting of the xCT-GSH synthetic system and Nrf2-ARE pathway in astrocytes. en-copyright= kn-copyright= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medical, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medical, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=glutathione kn-keyword=glutathione en-keyword=neuroprotection kn-keyword=neuroprotection en-keyword=parkinsonism kn-keyword=parkinsonism en-keyword=astrocyte kn-keyword=astrocyte en-keyword=region specificity kn-keyword=region specificity en-keyword=striatum kn-keyword=striatum en-keyword=mesencephalon kn-keyword=mesencephalon en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=Nrf2 kn-keyword=Nrf2 en-keyword=metallothionein kn-keyword=metallothionein en-keyword=serotonin 5-HT1A receptor kn-keyword=serotonin 5-HT1A receptor END start-ver=1.4 cd-journal=joma no-vol=39 cd-vols= no-issue= article-no= start-page=1511 end-page=1523 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021821 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neuroprotective Effects of Anti-high Mobility Group Box-1 Monoclonal Antibody Against Methamphetamine-Induced Dopaminergic Neurotoxicity en-subtitle= kn-subtitle= en-abstract= kn-abstract=High mobility group box-1 (HMGB1) is a ubiquitous non-histone nuclear protein that plays a key role as a transcriptional activator, with its extracellular release provoking inflammation. Inflammatory responses are essential in methamphetamine (METH)-induced acute dopaminergic neurotoxicity. In the present study, we examined the effects of neutralizing anti-HMGB1 monoclonal antibody (mAb) on METH-induced dopaminergic neurotoxicity in mice. BALB/c mice received a single intravenous administration of anti-HMGB1 mAb prior to intraperitoneal injections of METH (4 mg/kg x 2, at 2-h intervals). METH injections induced hyperthermia, an increase in plasma HMGB1 concentration, degeneration of dopaminergic nerve terminals, accumulation of microglia, and extracellular release of neuronal HMGB1 in the striatum. These METH-induced changes were significantly inhibited by intravenous administration of anti-HMGB1 mAb. In contrast, blood-brain barrier disruption occurred by METH injections was not suppressed. Our findings demonstrated the neuroprotective effects of anti-HMGB1 mAb against METH-induced dopaminergic neurotoxicity, suggesting that HMGB1 could play an initially important role in METH toxicity. en-copyright= kn-copyright= en-aut-name=MasaiKaori en-aut-sei=Masai en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaKeita en-aut-sei=Kuroda en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IsookaNami en-aut-sei=Isooka en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KikuokaRyo en-aut-sei=Kikuoka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiShinki en-aut-sei=Murakami en-aut-mei=Shinki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KamimaiSunao en-aut-sei=Kamimai en-aut-mei=Sunao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WangDengli en-aut-sei=Wang en-aut-mei=Dengli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=LiuKeyue en-aut-sei=Liu en-aut-mei=Keyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Medical Neurobiology, Okayama University Medical School kn-affil= affil-num=7 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil= kn-affil= affil-num=11 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=methamphetamine kn-keyword=methamphetamine en-keyword=dopamine neuron kn-keyword=dopamine neuron en-keyword=high mobility group box-1 kn-keyword=high mobility group box-1 en-keyword=hyperthermia kn-keyword=hyperthermia en-keyword=inflammation kn-keyword=inflammation en-keyword=neurotoxicity kn-keyword=neurotoxicity END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=3 article-no= start-page=598 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190130 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Region-Specific Neuroprotective Features of Astrocytes against Oxidative Stress Induced by 6-Hydroxydopamine en-subtitle= kn-subtitle= en-abstract= kn-abstract=In previous studies, we found regional differences in the induction of antioxidative molecules in astrocytes against oxidative stress, postulating that region-specific features of astrocytes lead region-specific vulnerability of neurons. We examined region-specific astrocytic features against dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) as an oxidative stress using co-culture of mesencephalic neurons and mesencephalic or striatal astrocytes in the present study. The 6-OHDA-induced reduction of mesencephalic dopamine neurons was inhibited by co-culturing with astrocytes. The co-culture of midbrain neurons with striatal astrocytes was more resistant to 6-OHDA than that with mesencephalic astrocytes. Furthermore, glia conditioned medium from 6-OHDA-treated striatal astrocytes showed a greater protective effect on the 6-OHDA-induced neurotoxicity and oxidative stress than that from mesencephalic astrocytes. The cDNA microarray analysis showed that the number of altered genes in both mesencephalic and striatal astrocytes was fewer than that changed in either astrocyte. The 6-OHDA treatment, apparently up-regulated expressions of Nrf2 and some anti-oxidative or Nrf2-regulating phase II, III detoxifying molecules related to glutathione synthesis and export in the striatal astrocytes but not mesencephalic astrocytes. There is a profound regional difference of gene expression in astrocytes induced by 6-OHDA. These results suggest that protective features of astrocytes against oxidative stress are more prominent in striatal astrocytes, possibly by secreting humoral factors in striatal astrocytes. en-copyright= kn-copyright= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Okumura-TorigoeNao en-aut-sei=Okumura-Torigoe en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MurakamiShinki en-aut-sei=Murakami en-aut-mei=Shinki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KitamuraYoshihisa en-aut-sei=Kitamura en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SendoToshiaki en-aut-sei=Sendo en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medical, Dental and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medical, Dental and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medical, Dental and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medical, Dental and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medical, Dental and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medical, Dental and Pharmaceutical Sciences kn-affil= en-keyword=astrocyte kn-keyword=astrocyte en-keyword=neuroprotection kn-keyword=neuroprotection en-keyword=region-specificity kn-keyword=region-specificity en-keyword=striatum kn-keyword=striatum en-keyword=mesencephalon kn-keyword=mesencephalon en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=6-hydroxydopamine kn-keyword=6-hydroxydopamine en-keyword=Nrf2 kn-keyword=Nrf2 en-keyword=phase II detoxifying molecules kn-keyword=phase II detoxifying molecules END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=12 article-no= start-page=2623 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201207 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neuron-Astrocyte Interactions in Parkinson's Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Parkinson's disease (PD) is the second most common neurodegenerative disease. PD patients exhibit motor symptoms such as akinesia/bradykinesia, tremor, rigidity, and postural instability due to a loss of nigrostriatal dopaminergic neurons. Although the pathogenesis in sporadic PD remains unknown, there is a consensus on the involvement of non-neuronal cells in the progression of PD pathology. Astrocytes are the most numerous glial cells in the central nervous system. Normally, astrocytes protect neurons by releasing neurotrophic factors, producing antioxidants, and disposing of neuronal waste products. However, in pathological situations, astrocytes are known to produce inflammatory cytokines. In addition, various studies have reported that astrocyte dysfunction also leads to neurodegeneration in PD. In this article, we summarize the interaction of astrocytes and dopaminergic neurons, review the pathogenic role of astrocytes in PD, and discuss therapeutic strategies for the prevention of dopaminergic neurodegeneration. This review highlights neuron-astrocyte interaction as a target for the development of disease-modifying drugs for PD in the future. en-copyright= kn-copyright= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=astrocyte kn-keyword=astrocyte en-keyword=Parkinson’s disease kn-keyword=Parkinson’s disease en-keyword=dopaminergic neuron kn-keyword=dopaminergic neuron en-keyword=neuroinflammation kn-keyword=neuroinflammation en-keyword=neuroprotection kn-keyword=neuroprotection en-keyword=alpha-synuclein kn-keyword=alpha-synuclein en-keyword=mitochondria kn-keyword=mitochondria END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=20698 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mirtazapine exerts astrocyte-mediated dopaminergic neuroprotection en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), is known to activate serotonin (5-HT) 1A receptor. Our recent study demonstrated that stimulation of astrocytic 5-HT1A receptors promoted astrocyte proliferation and upregulated antioxidative property in astrocytes to protect dopaminergic neurons against oxidative stress. Here, we evaluated the neuroprotective effects of mirtazapine against dopaminergic neurodegeneration in models of Parkinson's disease (PD). Mirtazapine administration attenuated the loss of dopaminergic neurons in the substantia nigra and increased the expression of the antioxidative molecule metallothionein (MT) in the striatal astrocytes of 6-hydroxydopamine (6-OHDA)-injected parkinsonian mice via 5-HT1A receptors. Mirtazapine protected dopaminergic neurons against 6-OHDA-induced neurotoxicity in mesencephalic neuron and striatal astrocyte cocultures, but not in enriched neuronal cultures. Mirtazapine-treated neuron-conditioned medium (Mir-NCM) induced astrocyte proliferation and upregulated MT expression via 5-HT1A receptors on astrocytes. Furthermore, treatment with medium from Mir-NCM-treated astrocytes protected dopaminergic neurons against 6-OHDA neurotoxicity, and these effects were attenuated by treatment with a MT-1/2-specific antibody or 5-HT1A antagonist. Our study suggests that mirtazapine could be an effective disease-modifying drug for PD and highlights that astrocytic 5-HT1A receptors may be a novel target for the treatment of PD. en-copyright= kn-copyright= en-aut-name=KikuokaRyo en-aut-sei=Kikuoka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KubotaNatsuki en-aut-sei=Kubota en-aut-mei=Natsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaedaMegumi en-aut-sei=Maeda en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KagawaDaiki en-aut-sei=Kagawa en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriyamaMasaaki en-aut-sei=Moriyama en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatoAsuka en-aut-sei=Sato en-aut-mei=Asuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MurakamiShinki en-aut-sei=Murakami en-aut-mei=Shinki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KitamuraYoshihisa en-aut-sei=Kitamura en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SendoToshiaki en-aut-sei=Sendo en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=11 article-no= start-page=4137 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cerebellar Blood Flow and Gene Expression in Crossed Cerebellar Diaschisis after Transient Middle Cerebral Artery Occlusion in Rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=Crossed cerebellar diaschisis (CCD) is a state of hypoperfusion and hypometabolism in the contralesional cerebellar hemisphere caused by a supratentorial lesion, but its pathophysiology is not fully understood. We evaluated chronological changes in cerebellar blood flow (CbBF) and gene expressions in the cerebellum using a rat model of transient middle cerebral artery occlusion (MCAO). CbBF was analyzed at two and seven days after MCAO using single photon emission computed tomography (SPECT). DNA microarray analysis and western blotting of the cerebellar cortex were performed and apoptotic cells in the cerebellar cortex were stained. CbBF in the contralesional hemisphere was significantly decreased and this lateral imbalance recovered over one week. Gene set enrichment analysis revealed that a gene set for "oxidative phosphorylation" was significantly upregulated while fourteen other gene sets including "apoptosis", "hypoxia" and "reactive oxygen species" showed a tendency toward upregulation in the contralesional cerebellum. MCAO upregulated the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the contralesional cerebellar cortex. The number of apoptotic cells increased in the molecular layer of the contralesional cerebellum. Focal cerebral ischemia in our rat MCAO model caused CCD along with enhanced expression of genes related to oxidative stress and apoptosis. en-copyright= kn-copyright= en-aut-name=KidaniNaoya en-aut-sei=Kidani en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HishikawaTomohito en-aut-sei=Hishikawa en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiramatsuMasafumi en-aut-sei=Hiramatsu en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishihiroShingo en-aut-sei=Nishihiro en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KinKyohei en-aut-sei=Kin en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakahashiYu en-aut-sei=Takahashi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MuraiSatoshi en-aut-sei=Murai en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiuKenji en-aut-sei=Sugiu en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YasuharaTakao en-aut-sei=Yasuhara en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=apoptosis kn-keyword=apoptosis en-keyword=cerebral blood flow kn-keyword=cerebral blood flow en-keyword=crossed cerebellar diaschisis kn-keyword=crossed cerebellar diaschisis en-keyword=ischemic stroke kn-keyword=ischemic stroke en-keyword=oxidative stress kn-keyword=oxidative stress END start-ver=1.4 cd-journal=joma no-vol=138 cd-vols= no-issue= article-no= start-page=111235 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200303 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of maternal bisphenol A diglycidyl ether exposure during gestation and lactation on behavior and brain development of the offspring en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bisphenol A diglycidyl ether (BADGE) is an epoxy resin used for the inner coating of canned food and beverages. BADGE can easily migrate from the containers and become a contaminant. In this study, we examined the effects of BADGE exposure to the dams on the behavioral, structural, and developmental abnormalities in the offspring. Female pregnant mice were fed with a diet containing BADGE (0.15 or 1.5 mg/kg/day) during gestation and lactation periods. In an open field test, the time spent in the corner area significantly increases in male mice of high-dose BADGE group at 5 weeks old. The histological analysis using offspring brain at postnatal day 1 delivered from BADGE (1.5 mg/kg/day)-treated dams demonstrates that positive signals of Forkhead box P2- and COUP-TF interacting protein 2 are restricted in each cortical layer, but not in the control brain. In addition, the maternal BADGE exposure reduces nestin-positive fibers of the radial glia and T-box transcription factor 2-positive intermediate progenitors in the inner subventricular zone. Furthermore, a direct BADGE exposure promotes neurite outgrowth and neuronal connection in the primary cultured cortical neurons. These data suggest that maternal BADGE exposure can accelerate neuronal differentiation in fetuses and induce anxiety-like behavior in juvenile mice. en-copyright= kn-copyright= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KikuokaRyo en-aut-sei=Kikuoka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IsookaNami en-aut-sei=Isooka en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakeshimaMika en-aut-sei=Takeshima en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SonobeKanau en-aut-sei=Sonobe en-aut-mei=Kanau kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AraiRei en-aut-sei=Arai en-aut-mei=Rei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FunakoshiHidemaru en-aut-sei=Funakoshi en-aut-mei=Hidemaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=QuinKyle E. en-aut-sei=Quin en-aut-mei=Kyle E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Smart Smart en-aut-sei=Smart en-aut-mei= Smart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ZenshoKazumasa en-aut-sei=Zensho en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Bisphenol A diglycidyl ether kn-keyword=Bisphenol A diglycidyl ether en-keyword=Epoxy resin kn-keyword=Epoxy resin en-keyword=Brain development kn-keyword=Brain development en-keyword=Neuronal differentiation kn-keyword=Neuronal differentiation en-keyword=Anxiety behavior kn-keyword=Anxiety behavior END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=6 article-no= start-page=e65983 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Transplantation of melanocytes obtained from the skin ameliorates apomorphine-induced abnormal behavior in rodent hemi-parkinsonian models en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tyrosinase, which catalyzes both the hydroxylation of tyrosine and consequent oxidation of L-DOPA to form melanin in melanocytes, is also expressed in the brain, and oxidizes L-DOPA and dopamine. Replacement of dopamine synthesis by tyrosinase was reported in tyrosine hydroxylase null mice. To examine the potential benefits of autograft cell transplantation for patients with Parkinson's disease, tyrosinase-producing cells including melanocytes, were transplanted into the striatum of hemi-parkinsonian model rats or mice lesioned with 6-hydroxydopamine. Marked improvement in apomorphine-induced rotation was noted at day 40 after intrastriatal melanoma cell transplantation. Transplantation of tyrosinase cDNA-transfected hepatoma cells, which constitutively produce L-DOPA, resulted in marked amelioration of the asymmetric apomorphine-induced rotation in hemi-parkinsonian mice and the effect was present up to 2 months. Moreover, parkinsonian mice transplanted with melanocytes from the back skin of black newborn mice, but not from albino mice, showed marked improvement in the apomorphine-induced rotation behavior up to 3 months after the transplantation. Dopamine-positive signals were seen around the surviving transplants in these experiments. Taken together with previous studies showing dopamine synthesis and metabolism by tyrosinase, these results highlight therapeutic potential of intrastriatal autograft cell transplantation of melanocytes in patients with Parkinson's disease. en-copyright= kn-copyright= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Francisco J.Diaz-Corrales en-aut-sei=Francisco J. en-aut-mei=Diaz-Corrales kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HigashiYouichirou en-aut-sei=Higashi en-aut-mei=Youichirou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NambaMasayoshi en-aut-sei=Namba en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OgawaNorio en-aut-sei=Ogawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=6 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences END start-ver=1.4 cd-journal=joma no-vol=68 cd-vols= no-issue=6 article-no= start-page=317 end-page=322 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=201412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Visualization of Astrocytic Primary Cilia in the Mouse Brain by Immunofluorescent Analysis Using the Cilia Marker Arl13b en-subtitle= kn-subtitle= en-abstract= kn-abstract=In vertebrates, almost all somatic cells extend a single immotile cilium, referred to as a primary cilium. Increasing evidence suggests that primary cilia serve as cellular antennae in many types of tissues by sensing chemical or mechanical stimuli in the milieu surrounding the cells. In rodents an antibody to adenylyl cyclase 3 (AC3) has been widely used to label the primary cilia of neurons in vivo by immunostaining, whereas the lack of markers for the primary cilia of astrocytes has made it difficult to observe astrocytic primary cilia in vivo. Here, we obtained a visualization of astrocytic primary cilia in the mouse brain. In the somatosensory cortex, a large portion of neurons and astrocytes at postnatal day 10 (P10), and of neurons at P56 had AC3-positive primary cilia, whereas only approx. one-half of the astrocytes in the P56 mice carried primary cilia weakly positive for AC3. In contrast, the majority of astrocytes had ADP-ribosylation factor-like protein 13B (Arl13b)-positive primary cilia in the somatosensory cortex and other brain regions of P56 mice. The lengths of astrocytic primary cilia positive for Arl13b varied among the brain regions. Our data indicate that Arl13b is a noteworthy marker of astrocytic primary cilia in the brain. en-copyright= kn-copyright= en-aut-name=KasaharaKyosuke en-aut-sei=Kasahara en-aut-mei=Kyosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiKo en-aut-sei=Miyoshi en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MurakamiShinki en-aut-sei=Murakami en-aut-mei=Shinki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=primary cilia kn-keyword=primary cilia en-keyword=astrocyte kn-keyword=astrocyte en-keyword=ADP-ribosylation factor-like protein 13B kn-keyword=ADP-ribosylation factor-like protein 13B END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=3 article-no= start-page=285 end-page=298 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=201410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neuroprotective Effects of Metallothionein Against Rotenone-Induced Myenteric Neurodegeneration in Parkinsonian Mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Parkinson's disease (PD) is a neurodegenerative disease with motor symptoms as well as non-motor symptoms that precede the onset of motor symptoms. Mitochondrial complex I inhibitor, rotenone, has been widely used to reproduce PD pathology in the central nervous system (CNS) and enteric nervous system (ENS). We reported previously that metallothioneins (MTs) released from astrocytes can protect dopaminergic neurons against oxidative stress. The present study examined the changes in MT expression by chronic systemic rotenone administration in the striatum and colonic myenteric plexus of C57BL mice. In addition, we investigated the effects of MT depletion on rotenone-induced neurodegeneration in CNS and ENS using MT-1 and MT-2 knockout (MT KO) mice, or using primary cultured neurons from MT KO mice. In normal C57BL mice, subcutaneous administration of rotenone for 6 weeks caused neurodegeneration, increased MT expression with astrocytes activation in the striatum and myenteric plexus. MT KO mice showed more severe myenteric neuronal damage by rotenone administration after 4 weeks than wild-type mice, accompanied by reduced astroglial activation. In primary cultured mesencephalic neurons from MT KO mice, rotenone exposure induced neurotoxicity in dopaminergic neurons, which was complemented by addition of recombinant protein. The present results suggest that MT seems to provide protection against neurodegeneration in ENS of rotenone-induced PD model mice. en-copyright= kn-copyright= en-aut-name=MurakamiShinki en-aut-sei=Murakami en-aut-mei=Shinki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SogawaNorio en-aut-sei=Sogawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyoshiKo en-aut-sei=Miyoshi en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Brain Sci affil-num=2 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Brain Sci affil-num=3 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Dent Pharmacol affil-num=4 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Brain Sci affil-num=5 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Brain Sci en-keyword=Parkinson's disease kn-keyword=Parkinson's disease en-keyword=Rotenone kn-keyword=Rotenone en-keyword=Enteric nervous system kn-keyword=Enteric nervous system en-keyword=Astrocytes kn-keyword=Astrocytes en-keyword=Metallothionein kn-keyword=Metallothionein END start-ver=1.4 cd-journal=joma no-vol=65 cd-vols= no-issue=5 article-no= start-page=279 end-page=285 dt-received= dt-revised= dt-accepted= dt-pub-year=2011 dt-pub=201110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Factors That Influence Primary Cilium Length en-subtitle= kn-subtitle= en-abstract= kn-abstract=Almost all mammalian cells carry one primary cilium that functions as a biosensor for chemical and mechanical stimuli. Genetic damages that compromise cilia formation or function cause a spectrum of disorders referred to as ciliapathies. Recent studies have demonstrated that some pharmacological agents and extracellular environmental changes can alter primary cilium length. Renal injury is a well-known example of an environmental insult that triggers cilia length modification. Lithium treatment causes primary cilia to extend in several cell types including neuronal cells;this phenomenon is likely independent of glycogen synthase kinase-3β inhibition. In renal epithelial cell lines, deflection of the primary cilia by fluid shear shortens them by reducing the intracellular cyclic AMP level, leading to a subsequent decrease in mechanosensitivity to fluid shear. Primary cilium length is also influenced by the dynamics of actin filaments and microtubules through the levels of soluble tubulin in the cytosol available for primary cilia extension. Thus, mammalian cells can adapt to the extracellular environment by modulating the primary cilium length, and this feedback system utilizing primary cilia might exist throughout the mammalian body. Further investigation is required concerning the precise molecular mechanisms underlying the control of primary cilium length in response to environmental factors. en-copyright= kn-copyright= en-aut-name=MiyoshiKo en-aut-sei=Miyoshi en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KasaharaKyosuke en-aut-sei=Kasahara en-aut-mei=Kyosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=primary cilium length kn-keyword=primary cilium length en-keyword=lithium kn-keyword=lithium en-keyword=cyclic AMP kn-keyword=cyclic AMP en-keyword=soluble tubulin kn-keyword=soluble tubulin en-keyword=intraflagellar transport kn-keyword=intraflagellar transport END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=4 article-no= start-page=219 end-page=223 dt-received= dt-revised= dt-accepted= dt-pub-year=2010 dt-pub=201008 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Imipramine and Lithium on the Suppression of Cell Proliferation in the Dentate Gyrus of the Hippocampus in Adrenocorticotropic Hormone-treated Rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=We examined the influence of chronic adrenocorticotropic hormone (ACTH) treatment on the number of Ki-67-positive cells in the dentate gyrus of the hippocampus in rats. ACTH treatment for 14 days decreased the number of such cells. The administration of imipramine or lithium alone for 14 days had no effect in saline-treated rats. The effect of ACTH was blocked by the administration of imipramine. Furthermore, the coadministration of imipramine and lithium for 14 days significantly increased the number of Ki-67-positive cells in both the saline and ACTH-treated rats. The coadministration of imipramine and lithium normalized the cell proliferation in the dentate gyrus of the hippocampus in rats treated with ACTH. en-copyright= kn-copyright= en-aut-name=DoiMaho en-aut-sei=Doi en-aut-mei=Maho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagamachiTomoko en-aut-sei=Nagamachi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShinomiyaKazuaki en-aut-sei=Shinomiya en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsunagaHisashi en-aut-sei=Matsunaga en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SendoToshiaki en-aut-sei=Sendo en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawasakiHiromu en-aut-sei=Kawasaki en-aut-mei=Hiromu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=GomitaYutaka en-aut-sei=Gomita en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitamuraYoshihisa en-aut-sei=Kitamura en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil=Department of Pharmaceutical Care and Health Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Department of Pharmacy, Okayama University Hospital affil-num=4 en-affil= kn-affil=Department of Pharmaceutical Care and Health Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Department of Pharmacy, Okayama University Hospital affil-num=6 en-affil= kn-affil=Department of Pharmacy, Okayama University Hospital affil-num=7 en-affil= kn-affil=Department of Clinical Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=8 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=9 en-affil= kn-affil=Shujitsu University School of Pharmacy affil-num=10 en-affil= kn-affil=Department of Pharmaceutical Care and Health Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=ACTH kn-keyword=ACTH en-keyword=imipramine kn-keyword=imipramine en-keyword=lithium kn-keyword=lithium en-keyword=proliferation kn-keyword=proliferation en-keyword=Ki-67 kn-keyword=Ki-67 END start-ver=1.4 cd-journal=joma no-vol=54 cd-vols= no-issue=6 article-no= start-page=275 end-page=280 dt-received= dt-revised= dt-accepted= dt-pub-year=2000 dt-pub=200012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immunophilin ligands prevent H2O2-induced apoptotic cell death by increasing glutathione levels in neuro 2A neuroblastoma cells. en-subtitle= kn-subtitle= en-abstract= kn-abstract=

We examined the effects of FK506 and its non-immunosuppressive derivative, GPI1046, on H2O2-induced reduction of cell viability and apoptotic cell death in Neuro 2A cells. Our results suggest that the protective properties of GPI1046 against H2O2-induced reduction of cell viability are equipotent with those of FK506 and may be mediated by increased intracellular concentrations of glutathione (GSH). In addition, both FK506 and GPI1046 prevented apoptotic cell death in Neuro 2A cells, although the antiapoptotic effect of FK506 was somewhat stronger than that of GPI1046. These findings suggest that non-immunosuppressive immunophilin ligands such as GPI1046 might be potentially useful in treatment of neurodegenerative diseases without serious side effects such as immune deficiency.

en-copyright= kn-copyright= en-aut-name=TanakaKen-ichi en-aut-sei=Tanaka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujitaNaoko en-aut-sei=Fujita en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OgawaNorio en-aut-sei=Ogawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University en-keyword=hydrogen peroxide kn-keyword=hydrogen peroxide en-keyword=immunophilin ligands kn-keyword=immunophilin ligands en-keyword=apoptosis kn-keyword=apoptosis en-keyword=glutathione kn-keyword=glutathione en-keyword=FK506 kn-keyword=FK506 en-keyword=GPI1046 kn-keyword=GPI1046 END start-ver=1.4 cd-journal=joma no-vol=45 cd-vols= no-issue=5 article-no= start-page=295 end-page=299 dt-received= dt-revised= dt-accepted= dt-pub-year=1991 dt-pub=199110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of beta-adrenergic blocking agents on specific binding of [3H]D-Ala2-Met5-enkephalinamide and [3H]naloxone. en-subtitle= kn-subtitle= en-abstract= kn-abstract=

To gain further insight into the central nervous system (CNS)-action of beta-adrenergic blocking agents (beta-blockers), we examined the effects of various kinds of beta-blockers on opioid receptors (Op-Rs) using radiolabeled receptor assay (RRA). We demonstrated that beta-blockers are competitively bound to Op-Rs in the CNS. Sodium index of beta-blockers in [3H]naloxone binding study indicated that beta-blockers had the mixed agonist-antagonist activity of opiates. The relative potency of beta-blockers in opioid RRA was negatively correlated with their membrane stabilizing activity. Neither beta-blocking activity nor intrinsic sympathomimetic activity was correlated with IC50 values of beta-blockers in opioid RRA. While it is widely accepted that beta-blockers have a tranquilizing activity, a part of the tranquilizing action of beta-blockers may be mediated through Op-Rs in the CNS. Although beta-blockers may have effects on their own receptors (beta-receptors) in the CNS, the more precise mechanisms of central action of these drugs must be further investigated.

en-copyright= kn-copyright= en-aut-name=TakayamaHaruhiko en-aut-sei=Takayama en-aut-mei=Haruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgawaNorio en-aut-sei=Ogawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirataHiroshi en-aut-sei=Hirata en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OguraToshio en-aut-sei=Ogura en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OtaZensuke en-aut-sei=Ota en-aut-mei=Zensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University affil-num=6 en-affil= kn-affil=Okayama University en-keyword=?-blocker kn-keyword=?-blocker en-keyword=opioid receptor kn-keyword=opioid receptor en-keyword=membrane stabilizing activity kn-keyword=membrane stabilizing activity en-keyword=sodium index kn-keyword=sodium index END start-ver=1.4 cd-journal=joma no-vol=58 cd-vols= no-issue=5 article-no= start-page=221 end-page=233 dt-received= dt-revised= dt-accepted= dt-pub-year=2004 dt-pub=200410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Quinone formation as dopaminergic neuron-specific oxidative stress in the pathogenesis of sporadic Parkinson's disease and neurotoxin-induced parkinsonism. en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by dopaminergic neuron-specific degeneration in the substantia nigra. A number of gene mutations and deletions have been reported to play a role in the pathogenesis of familial PD. Moreover, a number of pathological and pharmacological studies on sporadic PD and dopaminergic neurotoxin-induced parkinsonism have hypothesized that mitochondrial dysfunction, inflammation, oxidative stress, and dysfunction of the ubiquitin-proteasome system all play important roles in the pathogenesis and progress of PD. However, these hypotheses do not yet fully explain the mechanisms of dopaminergic neuron-specific cell loss in PD. Recently, the neurotoxicity of dopamine quinone formation by auto-oxidation of dopamine has been shown to cause specific cell death of dopaminergic neurons in the pathogenesis of sporadic PD and dopaminergic neurotoxin-induced parkinsonism. Furthermore, this quinone formation is closely linked to other representative hypotheses in the pathogenesis of PD. In this article, we mainly review recent studies on the neurotoxicity of quinone formation as a dopaminergic neuron-specific oxidative stress and its role in the etiology of PD, in addition to several neuroprotective approaches against dopamine quinone-induced toxicity.

en-copyright= kn-copyright= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Diaz-CorralesFrancisco J en-aut-sei=Diaz-Corrales en-aut-mei=Francisco J kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OgawaNorio en-aut-sei=Ogawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University en-keyword=dopamine quinone kn-keyword=dopamine quinone en-keyword=quinoprotein kn-keyword=quinoprotein en-keyword=Parkinson’sdisease kn-keyword=Parkinson’sdisease en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=neurotoxin kn-keyword=neurotoxin END start-ver=1.4 cd-journal=joma no-vol=55 cd-vols= no-issue=1 article-no= start-page=1 end-page=9 dt-received= dt-revised= dt-accepted= dt-pub-year=2001 dt-pub=200102 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Localization, regulation, and function of metallothionein-III/growth inhibitory factor in the brain. en-subtitle= kn-subtitle= en-abstract= kn-abstract=

The metallothionein (MT) family is a class of low molecular, intracellular, and cysteine-rich proteins with a high affinity for metals. Although the first of these proteins was discovered nearly 40 years ago, their functional significance remains obscure. Four major isoforms (MT-I, MT-II, MT-III, and MT-IV) have been identified in mammals. MT-I and MT-II are ubiquitously expressed in various organs including the brain, while expression of MT-III and MT-IV is restricted in specific organs. MT-III was detected predominantly in the brain, and characterized as a central nervous system-specific isomer. The role of MTs in the central nervous system has become an intense focus of scientific research. An isomer of MTs, MT-III, of particular interest, was originally discovered as a growth inhibitory factor, and has been found to be markedly reduced in the brain of patients with Alzheimer's disease and several other neurodegenerative diseases. MT-III fulfills unique biological roles in homeostasis of the central nervous system and in the etiology of neuropathological disorders.

en-copyright= kn-copyright= en-aut-name=AokiSogawa Chiharu en-aut-sei=Aoki en-aut-mei=Sogawa Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SogawaNorio en-aut-sei=Sogawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakanishiTohru en-aut-sei=Nakanishi en-aut-mei=Tohru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FurutaHiroaki en-aut-sei=Furuta en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OgawaNoriko en-aut-sei=Ogawa en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University affil-num=6 en-affil= kn-affil=Okayama University affil-num=7 en-affil= kn-affil=Okayama University en-keyword=neuroprotectin kn-keyword=neuroprotectin en-keyword=metal transport kn-keyword=metal transport en-keyword=localization kn-keyword=localization en-keyword=gene expression kn-keyword=gene expression en-keyword=neurodegenerative disease kn-keyword=neurodegenerative disease END start-ver=1.4 cd-journal=joma no-vol=62 cd-vols= no-issue=3 article-no= start-page=141 end-page=150 dt-received= dt-revised= dt-accepted= dt-pub-year=2008 dt-pub=200806 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dopaminergic neuron-specific oxidative stress caused by dopamine itself en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Oxidative stress, including the reactive oxygen or nitrogen species generated in the enzymatical oxidationor auto-oxidation of an excess amount of dopamine, is thought to play an important role in dopaminergic neurotoxicity. Dopamine and its metabolites containing 2 hydroxyl residues exert cytotoxicityin dopaminergic neuronal cells, primarily due to the generation of highly reactive dopamine and DOPA quinones. Dopamine and DOPA quinones may irreversibly alter protein function through the formation of 5-cysteinyl-catechols on the proteins. Furthermore, the quinone formation is closely linked to other representative hypotheses such as mitochondrial dysfunction, inflammation, oxidative stress, and dysfunction of the ubiquitin-proteasome system, in the pathogenesis of neurodegenerative diseases. Therefore, pathogenic effects of the dopamine quinone have recently focused on dopaminergicneuron-specific oxidative stress. In this article, we primarily review recent studies on the pathogenicity of quinone formation, in addition to several neuroprotective approaches against dopaminequinone-induced dysfunction of dopaminergic neurons.

en-copyright= kn-copyright= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=dopamine quinone kn-keyword=dopamine quinone en-keyword=quinoprotein kn-keyword=quinoprotein en-keyword=methamphetamine kn-keyword=methamphetamine en-keyword=Parkinson?s disease kn-keyword=Parkinson?s disease en-keyword=L-DOPA kn-keyword=L-DOPA END start-ver=1.4 cd-journal=joma no-vol=60 cd-vols= no-issue=6 article-no= start-page=299 end-page=309 dt-received= dt-revised= dt-accepted= dt-pub-year=2006 dt-pub=200612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Involvement of STAT3 in Bladder Smooth Muscle Hypertrophy Following Bladder Outlet Obstruction en-subtitle= kn-subtitle= en-abstract= kn-abstract=We examined the involvement of the signal transducer and activator of transcription 3 (STAT3) in bladder outlet obstruction (BOO)-induced bladder smooth muscle hypertrophy using a rat in vivo and in vitro study. BOO induced increases in bladder weight and bladder smooth muscle thickness 1 week after the operation. By using antibody microarrays, 64 of 389 proteins blotted on the array met our selection criteria of an INR value between > or = 2.0 and < or = 0.5. This result revealed up-regulation of transcription factors, cell cycle regulatory proteins, apoptosis-associated proteins and so on. On the other hand, down-regulation (INR value < or = 0.5) of proteins was not found. In a profiling study, we found an increase in the expression of STAT3. A significant increase in nuclear phosphorylated STAT3 expression was confirmed in bladder smooth muscle tissue by immunohistochemistry and Western blot analysis. Cyclical stretch-relaxation (1 Hz) at 120% elongation significantly increased the expression of STAT3 and of alpha-smooth muscle actin in primary cultured bladder smooth muscle cells. Furthermore, the blockade of STAT3 expression by the transfection of STAT3 small interfering RNA (siRNA) significantly prevented the stretch-induced increase in alpha-smooth muscle actin expression. These results suggest that STAT3 has an important role in the induction of bladder smooth muscle hypertrophy. en-copyright= kn-copyright= en-aut-name=FujitaOsamu en-aut-sei=Fujita en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YokoyamaTeruhiko en-aut-sei=Yokoyama en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OgawaNorio en-aut-sei=Ogawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KumonHiromi en-aut-sei=Kumon en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University affil-num=6 en-affil= kn-affil=Okayama University en-keyword=benign prostatic hyperplasia kn-keyword=benign prostatic hyperplasia en-keyword=bladder outlet obstruction kn-keyword=bladder outlet obstruction en-keyword=bladder smooth muscle kn-keyword=bladder smooth muscle en-keyword=signal transducer and activator of transcription 3 (STAT3) kn-keyword=signal transducer and activator of transcription 3 (STAT3) en-keyword=small interfering RNA (siRNA) kn-keyword=small interfering RNA (siRNA) END start-ver=1.4 cd-journal=joma no-vol=119 cd-vols= no-issue=3 article-no= start-page=235 end-page=239 dt-received= dt-revised= dt-accepted= dt-pub-year=2008 dt-pub=20080104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Quinone formation as a common neurotoxic factor in dopaminergic neurotoxicity induced by an excess amount of cytosolic dopamine kn-title=小胞外過剰ドパミンによるドパミン神経障害における共通因子としてのキノン体生成 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name=宮崎育子 kn-aut-sei=宮崎 kn-aut-mei=育子 aut-affil-num=1 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name=浅沼幹人 kn-aut-sei=浅沼 kn-aut-mei=幹人 aut-affil-num=2 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=Francisco J.Diaz-Corrales kn-aut-sei=Francisco J. kn-aut-mei=Diaz-Corrales aut-affil-num=3 ORCID= en-aut-name=MiyoshiKo en-aut-sei=Miyoshi en-aut-mei=Ko kn-aut-name=三好耕 kn-aut-sei=三好 kn-aut-mei=耕 aut-affil-num=4 ORCID= en-aut-name=OgawaNorio en-aut-sei=Ogawa en-aut-mei=Norio kn-aut-name=小川紀雄 kn-aut-sei=小川 kn-aut-mei=紀雄 aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 神経情報学 affil-num=2 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 神経情報学 affil-num=3 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 神経情報学 affil-num=4 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 神経情報学 affil-num=5 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 神経情報学 en-keyword=ドパミンキノン kn-keyword=ドパミンキノン en-keyword=パーキンソン病 kn-keyword=パーキンソン病 en-keyword=メタンフェタミン kn-keyword=メタンフェタミン en-keyword=キノン還元酵素 kn-keyword=キノン還元酵素 en-keyword=チロシナーゼ kn-keyword=チロシナーゼ END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=1992 dt-pub=19920331 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=カテコールアミン慢性欠乏状態のラット脳ムスカリン性M1受容体およびそのメッセンジャーRNAへの影響 kn-title=Effects of chronic catecholamine depletions on muscarinic M1-receptor and its mRNA in rat brain en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=淺沼幹人 kn-aut-sei=淺沼 kn-aut-mei=幹人 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END