2022 Fiscal Year Final Research Report
Relationship between myu-opioid receptor and neuronal alterations in the prefrontal cortex of subjects with schizophrenia
| Project/Area Number |
19H03580
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 52030:Psychiatry-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
紀本 創兵 奈良県立医科大学, 医学部, 講師 (00405391)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 死後脳 / パルブアルブミン / ソマトスタチン / アクチン関連 |
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| Outline of Final Research Achievements |
In the dorsolateral prefrontal cortex (DLPFC) of subjects with schizophrenia (SZ), alterations have been reported for cortical inhibitory neuron subtypes that express parvalbunmin (PV) or somatostatin (SST). The μ-type opioid receptor (MOR), which was shown to be enriched in PV and SST neurons and regulates neurotransmission by these neurons, was found to be upregulated in DLPFC of SZ subjects. Here, we tried to clarify 1) neuron types that express MOR, 2) MOR upregulation in other psychiatric diagnoses and 3) relationship between MOR upregulation and alterations of cortical neurons in SZ. We found that excitatory pyramidal neurons also express MOR and MOR was upregulated in major repression. Alteration in MOR expression was negatively correlated with expression of SST as well as RPC3 and CDC42, which regulate dendritic spines of pyramidal neurons, suggesting that MOR is associated with alterations of inhibitory as well as excitatory neurons in DLPFC of SZ subjects.
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| Free Research Field |
精神神経科学
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| Academic Significance and Societal Importance of the Research Achievements |
統合失調症では、認知機能に中心的役割を果たす前頭前野において、抑制性介在ニューロンに属するPVニューロン及びSSTニューロン、そして興奮性の錐体ニューロンの変化が報告されている。本研究では、統合失調症の前頭前野で発現の増加が認められるμ型オピオイド受容体（MOR）が、これらのニューロンに広く発現すること、SSTニューロン及び錐体ニューロンの変化と負の相関を示すことが明らかになった。統合失調症におけるMORの増加は、SSTニューロンおよび錐体ニューロンの変化の分子メカニズムに関連すると考えられる。本研究の成果は難治性の認知機能障害の病態メカニズムとそれに基づいた治療法の開発に役立つ可能性がある。
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