ID | 61530 |
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Asanuma, Masato
Department of Medical Neurobiology, Okayama University Graduate School of Medical, Dental and Pharmaceutical Sciences
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Okumura-Torigoe, Nao
Department of Clinical Pharmacy, Okayama University Graduate School of Medical, Dental and Pharmaceutical Sciences
Miyazaki, Ikuko
Department of Medical Neurobiology, Okayama University Graduate School of Medical, Dental and Pharmaceutical Sciences
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Murakami, Shinki
Department of Medical Neurobiology, Okayama University Graduate School of Medical, Dental and Pharmaceutical Sciences
Kitamura, Yoshihisa
Department of Clinical Pharmacy, Okayama University Graduate School of Medical, Dental and Pharmaceutical Sciences
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Sendo, Toshiaki
Department of Clinical Pharmacy, Okayama University Graduate School of Medical, Dental and Pharmaceutical Sciences
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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.
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Keywords | astrocyte
neuroprotection
region-specificity
striatum
mesencephalon
oxidative stress
6-hydroxydopamine
Nrf2
phase II detoxifying molecules
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Published Date | 2019-01-30
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Publication Title |
International Journal of Molecular Sciences
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Volume | volume20
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Issue | issue3
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Publisher | MDPI
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Start Page | 598
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ISSN | 1422-0067
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NCID | AA12038549
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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File Version | publisher
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PubMed ID | |
DOI | |
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Related Url | isVersionOf https://doi.org/10.3390/ijms20030598
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License | https://creativecommons.org/licenses/by/4.0/
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Funder Name |
Japan Society for the Promotion of Science
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助成番号 | JP24111533
JP22590934
JP25461279
JP16K09673
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