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2023 Fiscal Year Final Research Report

In vitro, in vivo functions and involvement in schizophrenia of lipid modifying enzyme that shows activity-dependent expression

Research Project

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Project/Area Number 21K06375
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 46010:Neuroscience-general-related
Research InstitutionKagoshima University

Principal Investigator

Haraguchi Misako  鹿児島大学, 医歯学域医学系, 准教授 (10244229)

Co-Investigator(Kenkyū-buntansha) 奥野 浩行  鹿児島大学, 医歯学域医学系, 教授 (80272417)
城山 優治  鹿児島大学, 医歯学域医学系, 助教 (90456195)
Project Period (FY) 2021-04-01 – 2024-03-31
Keywordszdhhc18 / 神経活動依存的
Outline of Final Research Achievements

Palmitoylation of proteins plays important role on neuronal function. Among palmitoyl transferase, authors found that expression of zdhhc18 depend on neuronal activity. In this study, authors made zdhhc18 Knockout mice to determine the physiological role and performed the morphological analysis of neuronal cells and behavioral analysis of mice. We injected AAV vectors that express fluorescent protein into dentate gyrus of Hippocampus of KO and Wild type mice and compare the length and complexities of granulocytes. Zdhhc18 KO mice did not display decrease of pre-pulse inhibition (that is typical phenotype of schizophrenia). Zdhhc18 KO mice showed reduced anxiety in open field test.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

タンパク質のパルミトイル化は神経機能に重要な役割を果たしており、大規模ゲノム解析ではいくつかのパルミトイル化酵素遺伝子の変異と統合失調症への関連が示唆されている。特にZdhhc18は活動依存性を示し統合失調症との関連も示唆されていた。本研究においては統合失調症に特徴的な行動プレパルスインヒビションが見られないことを確認した。一方当研究室においてオープンフィールド試験を行いKOマウスの不安が低下することを確認した。これはバッテリー試験を依頼した藤田医科大学でも再現性を得ておりZDHHC18 が不安を担う神経機能に関わることが確認できた。

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Published: 2025-01-30  

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