Evaluation of effect of thyroid hormone on neuronal injuries following transient cerebral ischemia in mice

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09336
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Teikyo University
• Principal Investigator: Doshi Masaru 帝京大学, 薬学部, 講師 (30392385)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 甲状腺ホルモン / マウス脳虚血モデル / 海馬神経細胞死

Outline of Final Research Achievements

In mice, global cerebral ischemia (GCI) causes neuronal injuries after reperfusion in the hippocampus. In this study, we examined the effect of T3 administration on DNA fragmentation induced by neuronal death and the activation of inflammatory cells such as astrocytes and microglia in the hippocampus following GCI. The content of nucleosomes generated by DNA fragmentation in the hippocampus was increased by GCI and further increased by T3 administration. The protein expression levels of GFAP and Iba1 in the hippocampus were also increased by GCI and further increased by T3 administration. Our results indicate that T3 administration aggravates GCI-reperfusion injury in mice. We also demonstrated that T3 administration inhibited the gene induction of TGF-β1 in the hippocampus following GCI. Therefore, the inhibition of TGF-β1 expression might be one of the reasons for aggravation of neuronal injuries by additional T3 administration.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

本研究ではT3投与がマウス脳虚血再潅流後の海馬神経傷害を悪化させることを明らかにした。つまり、体内のT3濃度が高いと脳卒中後遺症がより重度になる可能性が示唆された。一方、脳虚血は脳外科手術などでもみられるため、今回の研究成果は、周術期の脳神経保護の観点から、甲状腺機能亢進症患者や甲状腺ホルモン製剤を服用している甲状腺機能低下症患者の血中T3濃度に対する充分な管理が必要であることを示唆するものであると考えられる。