Light-at-night exposure affects brain development through pineal allopregnanolone-dependent mechanisms
- Waseda University, Japan
- Kyushu University, Japan
- Showa University School of Medicine, Japan
- University of Toyama, Japan
- Shizuoka University, Japan
- Ehime University, Japan
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files for Figures 1-10 have been deposited to Dryad DOI: https://doi.org/10.5061/dryad.k6g8b53
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Data from: Light-at-night exposure affects brain development through pineal allopregnanolone-dependent mechanismsDryad Digital Repository, doi:10.5061/dryad.k6g8b53.
Article and author information
Author details
Funding
Japan Society for the Promotion of Science (15K18571)
- Shogo Haraguchi
Takeda Science Foundation
- Shogo Haraguchi
Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care
- Shogo Haraguchi
Kao Corporation
- Shogo Haraguchi
Naito Foundation
- Shogo Haraguchi
Narishige Zoological Science Foundation
- Shogo Haraguchi
Yamaguchi Endocrine Research Foundation
- Shogo Haraguchi
Suntory Foundation for Life Sciences
- Shogo Haraguchi
Japan Society for the Promotion of Science (22227002)
- Kazuyoshi Tsutsui
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: The experimental protocols (2011-A090, 2012-A003, 2013-A010, 2014-A063, 2015-A012, 29M050, 30M047) were in accordance with the Guide for the Care and Use of Laboratory Animals of Waseda University or Showa University, Japan.
Copyright
© 2019, Haraguchi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Light-at-night exposure affects brain development through pineal allopregnanolone-dependent mechanisms
eLife 8:e45306.
https://doi.org/10.7554/eLife.45306
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