Primary cilia safeguard cortical neurons in neonatal mouse forebrain from environmental stress-induced dendritic degeneration

Seiji Ishii, Toru Sasaki, Shahid Mohammad, Hye Hwang, Edwin Tomy, Fahad Somaa, Nobuyuki Ishibashi, Hideyuki Okano, Pasko Rakic, Kazue Hashimoto-Torii, Masaaki Torii

研究成果: Article査読

1 被引用数 (Scopus)

抄録

The developing brain is under the risk of exposure to a multitude of environmental stressors. While perinatal exposure to excessive levels of environmental stress is responsible for a wide spectrum of neurological and psychiatric conditions, the developing brain is equipped with intrinsic cell protection, the mechanisms of which remain unknown. Here we show, using neonatal mouse as a model system, that primary cilia, hair-like protrusions from the neuronal cell body, play an essential role in protecting immature neurons from the negative impacts of exposure to environmental stress. More specifically, we found that primary cilia prevent the degeneration of dendritic arbors upon exposure to alcohol and ketamine, two major cell stressors, by activating cilia-localized insulin-like growth factor 1 receptor and downstream Akt signaling. We also found that activation of this pathway inhibits Caspase-3 activation and caspase-mediated cleavage/fragmentation of cytoskeletal proteins in stress-exposed neurons. These results indicate that primary cilia play an integral role in mitigating adverse impacts of environmental stressors such as drugs on perinatal brain development.

本文言語English
論文番号e2012482118
ジャーナルProceedings of the National Academy of Sciences of the United States of America
118
1
DOI
出版ステータスPublished - 2021 1 5

ASJC Scopus subject areas

  • 一般

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