Exploring new molecular to depression vulnerability formation in striatum

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07190
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Setsunan University
• Principal Investigator: Uno Kyosuke 摂南大学, 薬学部, 講師 (30608774)
• Co-Investigator(Kenkyū-buntansha): 高崎 一朗 富山大学, 学術研究部工学系, 准教授 (00397176)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: うつ / AAV / 線条体

Outline of Final Research Achievements

After exposure to social defeat stress, three groups of stress-sensitive mice, stress-resistant mice, and control mice were obtained. Striatum was removed from these mice and gene expression analysis was performed using a next-generation sequencer. From the obtained results, about 10 types of stress vulnerability factors were extracted, and one of the most likely gene X was determined. Next, this gene X was cloned and recombined into a vector associated with GFP, and then an adeno-associated virus of the gene was prepared. When the prepared virus was infected with primary cultured nerve cells, protein expression was confirmed, and then injected into the mouse striatum, and the same stress was applied, almost no stress-sensitive group was observed.

Free Research Field

神経精神薬理

Academic Significance and Societal Importance of the Research Achievements

現在、うつ病や統合失調症を含む精神疾患の患者数は年々増加しており、うつ病は精神疾患の中で最も患者数が多い疾患とされている。世界精神保健調査（WMH）によると我が国におけるうつ病の生涯有病率は人口の6.6％、12か月有病率は2.1％である。また、うつ病の主症状には抑うつ気分、無関心、食欲減退、睡眠障害および自殺企図などが挙げられ、うつ病が社会に与える影響は大きいことといえる。今回見つかった候補遺伝子がうつ脆弱性決定因子であれば、今後この遺伝子をターゲットとした創薬に結び付き、うつ病発症のリスクあるいは重症化を減弱することが可能と考えられる。