Functional analysis of HDAC3 in hypothyroidism and study of genome compartmentalization by a new method.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08569
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Niigata College of Nursing (2023); Gunma University (2021-2022)
• Principal Investigator: Sumiyasu Ishii 新潟県立看護大学, 看護学部, 教授 (60638112)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: HDAC3 / 甲状腺ホルモン / 小脳

Outline of Final Research Achievements

We aimed to study whether the cerebellar developmental defects induced by perinatal hypothyroidism can be rescued by treatment with a specific inhibitor of histone deacetylase (HDAC) 3. The treatment with the HDAC3 inhibitor alleviated the cerebellar morphological defects and motor coordination defects in hypothyroid mice. In addition, the administration of the inhibitor increased the levels of mRNA and histone acetylation of cerebellar thyroid hormone-responsive genes. These findings indicate that HDAC3 plays an important role in the cerebellar developmental defects induced by perinatal hypothyroidism.

Free Research Field

内分泌代謝分野

Academic Significance and Societal Importance of the Research Achievements

本研究の結果より、周産期甲状腺機能低下症において、HDAC3が甲状腺ホルモン応答遺伝子のヒストンを脱アセチル化して転写を抑制することにより小脳発達障害に重要な役割を果たしているという病態が明らかになった。そのため、HDAC3阻害剤は、甲状腺ホルモン応答遺伝子のヒストンをアセチル化と転写を刺激することにより、甲状腺機能低下症に起因する小脳障害に対する新規治療薬として応用できる可能性があると考えられる。