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

Haraguchi, Shogo; Kamata, Masaki; Tokita, Takuma; Tashiro, Kei-Ichiro; Sato, Miku; Nozaki, Mitsuki; Okamoto-Katsuyama, Mayumi; Shimizu, Isao et al. · Elife · 2019

basic_science · Level V

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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 <i>Adcyap1</i> gene that produces PACAP, with subsequent Purkinje cell death. Taken together, pineal ALLO mediated the effect of light on early cerebellar development in chicks.

Medical subject headings