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ID 61251
フルテキストURL
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著者
Kikuoka, Ryo Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Miyazaki, Ikuko Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ORCID Kaken ID publons researchmap
Kubota, Natsuki Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Maeda, Megumi Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kagawa, Daiki Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Moriyama, Masaaki Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Sato, Asuka Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Murakami, Shinki Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kitamura, Yoshihisa Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ORCID Kaken ID publons researchmap
Sendo, Toshiaki Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaken ID publons researchmap
Asanuma, Masato Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaken ID publons researchmap
抄録
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.
発行日
2020-11-26
出版物タイトル
Scientific Reports
10巻
1号
出版者
Nature Research
開始ページ
20698
ISSN
2045-2322
資料タイプ
学術雑誌論文
言語
English
OAI-PMH Set
岡山大学
著作権者
© The Author(s) 2020
論文のバージョン
publisher
PubMed ID
DOI
Web of Science KeyUT
関連URL
isVersionOf https://doi.org/10.1038/s41598-020-77652-4
ライセンス
http://creat iveco mmons .org/licen ses/by/4.0/
助成機関名
文部科学省
助成番号
24111533