Significance and molecular mechanisms of primary cilia controlling the stress critical period of cortical development.

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07829
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Keio University
• Principal Investigator: ISHII Seiji 慶應義塾大学, 医学部(信濃町), 助教 (50468493)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 大脳皮質 / 一次繊毛 / 環境ストレス / アルコール / 麻酔薬

Outline of Final Research Achievements

It has been suggested that there is a "critical period" in mouse cortical neurons immediately after birth, when they become vulnerable to environmental stress. On the other hand, primary cilia are still largely absent in neurons of the mouse cerebral cortex during the embryonic period, and are known to mature by the end of the critical period for stress tolerance after birth. Layer 5 neurons in the cerebral cortex of mice lacking primary cilia that had been exposed to environmental stress on postnatal day 7 was examined and found that speckled active caspase-3 was detected in large numbers, especially in layer 5 neurons of the cerebral cortex. They also found that IGF-1 receptors accumulated on the primary ciliary membranes of neurons in the cerebral cortex and activated the PI3K/Akt signaling pathway.

Free Research Field

病態神経科学

Academic Significance and Societal Importance of the Research Achievements

一次繊毛の形成、機能異常に起因すると考えられている遺伝性疾患は総称して繊毛病（シリオパチー）と呼ばれ、網膜色素変性症、嚢胞腎、多指症、水頭症、不妊、肥満など、多岐にわたる症状を呈することが知られている。本研究において「環境ストレスに対する一次繊毛を介した臨界期中枢神経系の防御機構」の分子基盤を明らかにする事で、一次繊毛を介した環境ストレス応答機構という新たな概念を提唱することができ、一次繊毛に対する理解が深まるものと期待される。本研究において得られた知見は、今後、多岐にわたる繊毛病の発症メカニズムの理解や新たな治療法への応用に貢献できるものと考えられる。