A phase advance of the light-dark cycle stimulates production of BDNF, but not of other neurotrophins, in the adult rat cerebral cortex: association with the activation of CREB
A phase advance of the light-dark cycle stimulates production of BDNF, but not of other neurotrophins, in the adult rat cerebral cortex: association with the activation of CREB
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DOI：
10.1111/j.1471-4159.2008.05565.x
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发表时间：
2008-09-01
影响因子：
4.7
通讯作者：
Nagata, Koh-ichi
中科院分区：
文献类型：
--
作者：
Katoh-Semba, Ritsuko;Tsuzuki, Masako;Nagata, Koh-ichi
脑源性神经营养因子（BDNF）表达的昼夜节律变化表明BDNF参与多种生物过程中昼夜节律的调节。然而，目前尚不清楚哪些大脑区域会因外部光输入而改变其 BDNF 水平。因此，在成年雄性大鼠的选定大脑区域中，我们研究了昼夜变化以及光暗周期的单个八小时相位提前对 BDNF 和其他神经营养因子水平的影响。小脑、海马体和包含视觉皮层 (VCX) 的大脑皮层的 BDNF 蛋白水平显示出昼夜变化，VCX 的 NT-3 水平也显示出昼夜变化。在VCX和包含内嗅皮层和杏仁核（ECX）的区域中，BDNF蛋白水平在相位提前12小时后增加，而BDNF mRNA水平在VCX中显着增加，在ECX中4小时后略有增加。然而，一周后，在检查的 13 个大脑区域中，有 8 个区域的 BDNF 蛋白水平降低了。 ECX 和 VCX 中的 BDNF 水平在光照饲养和黑暗饲养之间存在显着差异，而甲状腺功能减退状态则没有产生影响。环AMP反应元件结合蛋白（CREB）是BDNF的转录因子，ECX和VCX的相位超前极大地激活了该蛋白，这表明CREB介导的BDNF合成途径的存在对外部光输入有反应。
Circadian variation in the expression of brain-derived neurotrophic factor (BDNF) indicates that BDNF is involved in the regulation of diurnal rhythms in a variety of biological processes. However, it is still unclear which brain regions alter their BDNF levels in response to external light input. Therefore, in selected brain regions of adult male rats, we investigated diurnal variation, as well as the effects of a single eight-hour phase advance of the light-dark cycle, on the levels of BDNF and of other neurotrophins. The cerebellum, hippocampus and cerebral cortex containing visual cortex (VCX) showed diurnal variation in BDNF protein levels and the VCX also in NT-3 levels. In the VCX and the region containing the entorhinal cortex and amygdala (ECX), BDNF protein levels were increased 12 h after the phase advance, while BDNF mRNA levels were increased significantly in the VCX and slightly in the ECX after 4 h. After one week, however, BDNF protein levels were reduced in eight brain regions out of 13 examined. BDNF levels in the ECX and VCX were significantly different between light rearing and dark rearing, while a hypothyroid status did not produce an effect. Cyclic AMP responsive element-binding protein (CREB), a transcription factor for BDNF, was greatly activated by the phase advance in the ECX and VCX, suggesting the existence of CREB-mediated pathways of BDNF synthesis that are responsive to external light input.