2022 Fiscal Year Final Research Report

Psychiatric comorbidity that metabolic tolerance is involved and sialylation

Research Project

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Project/Area Number	20K06451
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 42030:Animal life science-related
Research Institution	Kyoto Sangyo University
Principal Investigator	Kato Keiko 京都産業大学, 生命科学部, 教授 (90252684)
Co-Investigator(Kenkyū-buntansha)	藤田明子京都産業大学, 生命科学部, 研究員 (60535003) 黒坂光京都産業大学, 生命科学部, 教授 (90186536)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	シアル酸転移酵素 / うつ・不安症 / 側頭葉てんかん / 扁桃体 / 視床 / 代謝 / アルカリフォスファターゼ
Outline of Final Research Achievements	The global prevalence of epilepsy, depression, anxiety, epilepsy, and schizophrenia show comorbidity with each other. Further, metabolic disorders including the side effects of drugs, show high comorbidity with psychiatric disorders, such as obesity and cardiovascular diseases. Genome-wide association studies (GWAS) catalog has previously indicated that single-nucleotide polymorphisms of ST3GAL4 are associated with alkaline phosphatase (ALP), proteins, and cholesterol in the blood. Previous research has shown that mouse St3Gal4 regulates the onset of epilepsy, depression, and anxiety through its expression levels in the thalamic neurons. This study demonstrated that mouse St3Gal4 is also associated with metabolic parameters similar to human ST3Gal4. This study suggests that St3Gal4 deficient mice help to investigate how to incident comorbidity between emotional behaviors and metabolic aberration.
Free Research Field	実験動物学，神経化学，糖質生物学
Academic Significance and Societal Importance of the Research Achievements	本研究は，シアル酸転移酵素・St3Gal4が担当するシアル酸修飾が，代謝変化を伴う情動変化を示すこと，そしてこの変化はヒトにも外挿できる可能性を示唆している。これまでに， St3Gal4欠損マウスが示す不安様行動の亢進が，血中ALP(アルカリフォスファターゼ)値の上昇と正の相関を示し，さらに，視床におけるALP活性低下と負の相関を示すことを見つけた。St3Gal4欠損マウスは，情動機能と代謝疾患の共存に関与するモデルであることを示すことができたことから，精神疾患と代謝疾患の共存症の発症機構を研究するモデルマウスを提案することができた。