Light-at-night exposure affects brain development through pineal allopregnanolone-dependent mechanisms
Light-at-night exposure affects brain development through pineal allopregnanolone-dependent mechanisms
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DOI：
10.7554/elife.45306
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发表时间：
2019-09
期刊：
影响因子：
7.7
通讯作者：
S. Haraguchi;Masaki Kamata;Takuma Tokita;Kei-ichiro Tashiro;Miku Sato;Mitsuki Nozaki;Mayumi Okamoto-Katsuyama;Isao Shimizu;G. Han;V. S. Chowdhury;X. Lei;T. Miyazaki;Joo-Ri Kim-Kaneyama;T. Nakamachi;K. Matsuda;H. Ohtaki;T. Tokumoto;T. Tachibana;A. Miyazaki;K. Tsutsui
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文献类型：
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作者：
S. Haraguchi;Masaki Kamata;Takuma Tokita;Kei-ichiro Tashiro;Miku Sato;Mitsuki Nozaki;Mayumi Okamoto-Katsuyama;Isao Shimizu;G. Han;V. S. Chowdhury;X. Lei;T. Miyazaki;Joo-Ri Kim-Kaneyama;T. Nakamachi;K. Matsuda;H. Ohtaki;T. Tokumoto;T. Tachibana;A. Miyazaki;K. Tsutsui
环境光条件影响小脑发育的分子机制还不完全清楚。我们发现，昼夜节律的破坏，在夜间光诱导浦肯野细胞死亡，通过松果体allopregnanolone（ALLO）的活动在小鸡的早期生活。在生命早期，夜间光照导致松果体ALLO合成的昼夜变化丧失，并导致小脑浦肯野细胞死亡，这被每天注射ALLO抑制。松果体ALLO合成的昼夜变化的损失不仅诱导减少垂体腺苷酸环化酶激活多肽（PACAP），一种神经保护激素，但也转录抑制小脑Adcyap1基因产生PACAP，随后浦肯野细胞死亡。两者合计，松果体ALLO介导光对雏鸡小脑早期发育的影响。
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.