Ethanol modulates mammalian circadian clock phase resetting through extrasynaptic GABA receptor activation.
Ethanol modulates mammalian circadian clock phase resetting through extrasynaptic GABA receptor activation.
复制标题
DOI：
10.1016/j.neuroscience.2009.08.020
复制
发表时间：
2009-12-01
期刊：
影响因子：
3.3
通讯作者：
Prosser, R. A.
中科院分区：
文献类型：
--
作者：
McElroy, B.;Zakaria, A.;Glass, J. D.;Prosser, R. A.
乙醇调节多种神经递质系统的作用，包括GABA。然而，其对GABA信号传导的增强作用通常仅在高浓度下可见。相比之下，虽然GABA是视交叉上核（SCN）昼夜节律钟中的一种重要神经递质，但我们发现乙醇在低浓度（<50 mM）下可调节时钟相位重置。一种可能的解释是，乙醇通过激活含有δ亚基的GABAA受体（GABAAδ受体）增强SCN中的GABA能信号传导，该受体对低乙醇浓度敏感。因此，我们研究了乙醇是否作用于SCN中的GABAAδ受体。在这里，我们表明，急性应用GABAAδ受体拮抗剂，RO 15 -4513，小鼠下丘脑切片含有SCN防止乙醇抑制夜间谷氨酸诱导（光样）的生物钟相位延迟。地西泮可增强GABAAγ受体的活性，但不调节这些相移。此外，我们发现RO 15 -4513可以防止乙醇增强昼夜节律钟的日间血清素（非光）相位提前。此外，地西泮在白天单独使用时会使SCN生物钟相位提前，而乙醇本身在当时没有影响。这些数据支持乙醇作用于SCN中的GABAAδ受体以调节光和非光生物钟相位重置的假设。它们还揭示了不同GABAA受体亚型在生物钟相位调节中的不同调节作用。
Ethanol modulates the actions of multiple neurotransmitter systems, including GABA. However, its enhancing effects on GABA signaling typically are seen only at high concentrations. In contrast, although GABA is a prominent neurotransmitter in the circadian clock of the suprachiasmatic nucleus (SCN), we see ethanol modulation of clock phase resetting at low concentrations (<50 mM). A possible explanation is that ethanol enhances GABAergic signaling in the SCN through activating GABAA receptors that contain the δ subunit (GABAAδ receptors), which are sensitive to low ethanol concentrations. Therefore, we investigated whether ethanol acts on GABAAδ receptors in the SCN. Here we show that acute application of the GABAAδ receptor antagonist, RO15-4513, to mouse hypothalamic slices containing the SCN prevents ethanol inhibition of nighttime glutamate-induced (photic-like) phase delays of the circadian clock. Diazepam, which enhances activity of GABAAγ receptors, does not modulate these phase shifts. Moreover, we find that RO15-4513 prevents ethanol enhancement of daytime serotonergic (non-photic) phase advances of the circadian clock. Furthermore, diazepam phase-advances the SCN circadian clock when applied alone in the daytime, while ethanol has no effect by itself at that time. These data support the hypothesis that ethanol acts on GABAAδ receptors in the SCN to modulate photic and non-photic circadian clock phase resetting. They also reveal distinct modulatory roles of different GABAA receptor subtypes in circadian clock phase regulation.
登录
查看更多内容
影响因子：
2.3
作者：
Botta, Paolo;Radcliffe, Richard A.;Valenzuela, C. Fernando
通讯作者：
Valenzuela, C. Fernando
影响因子：
3.3
作者：
Belenky, MA;Sagiv, N;Yarom, Y
通讯作者：
Yarom, Y
影响因子：
1.7
作者：
Gamble, KL;Novak, CM;Albers, HE
通讯作者：
Albers, HE
影响因子：
3.5
作者：
Ehlen, J. Christopher;Novak, Colleen M.;Albers, H. Elliott
通讯作者：
Albers, H. Elliott
影响因子：
56.9
作者：
DING, JM;CHEN, D;GILLETTE, MU
通讯作者：
GILLETTE, MU