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

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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. Taken together, pineal ALLO mediated the effect of light on early cerebellar development in chicks

Original languageEnglish
JournaleLife
Volume8
Publication statusPublished - Sep 2019

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All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Haraguchi, S., Kamata, M., Tokita, T., Tashiro, K. I., Sato, M., Nozaki, M., ... Tsutsui, K. (2019). Light-at-night exposure affects brain development through pineal allopregnanolone-dependent mechanisms. eLife, 8.