Light-at-night exposure affects brain development through pineal allopregnanolone-dependent mechanisms

Shogo Haraguchi, Masaki Kamata, Takuma Tokita, Kei Ichiro Tashiro, Miku Sato, Mitsuki Nozaki, Mayumi Okamoto-Katsuyama, Isao Shimizu, Guofeng Han, Vishwajit S. Chowdhury, Xiao Feng Lei, Takuro Miyazaki, Joo Ri Kim-Kaneyama, Tomoya Nakamachi, Kouhei Matsuda, Hirokazu Ohtaki, Toshinobu Tokumoto, Tetsuya Tachibana, Akira Miyazaki, Kazuyoshi Tsutsui

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

The molecular mechanisms by which environmental light conditions affect cerebellar development are incompletely understood. We showed that circadian disruption by light-at-night induced Purkinje cell death through pineal allopregnanolone (ALLO) activity during early life in chicks. Light-at-night caused the loss of diurnal variation of pineal ALLO synthesis during early life and led to cerebellar Purkinje cell death, which was suppressed by a daily injection of ALLO. The loss of diurnal variation of pineal ALLO synthesis induced not only reduction in pituitary adenylate cyclase-activating polypeptide (PACAP), a neuroprotective hormone, but also transcriptional repression of the cerebellar Adcyap1 gene that produces PACAP, with subsequent Purkinje cell death.

Original languageEnglish
JournaleLife
Volume8
DOIs
Publication statusPublished - Sept 2019

All Science Journal Classification (ASJC) codes

  • General Immunology and Microbiology
  • General Biochemistry,Genetics and Molecular Biology
  • General Neuroscience

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