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The Excitatory Effects of GABA within the Suprachiasmatic Nucleus: Regulation of Na-K-2Cl Cotransporters (NKCCs) by Environmental Lighting Conditions.
Journal of Biological Rhythms ( IF 2.9 ) Pub Date : 2020-05-14 , DOI: 10.1177/0748730420924271
John K McNeill 1 , James C Walton 1 , Vitaly Ryu 1 , H Elliott Albers 1
Affiliation  

The suprachiasmatic nucleus (SCN) contains a pacemaker that generates circadian rhythms and entrains them with the 24-h light-dark cycle (LD). The SCN is composed of 16,000 to 20,000 heterogeneous neurons in bilaterally paired nuclei. γ-amino butyric acid (GABA) is the primary neurochemical signal within the SCN and plays a key role in regulating circadian function. While GABA is the primary inhibitory neurotransmitter in the brain, there is now evidence that GABA can also exert excitatory effects in the adult brain. Cation chloride cotransporters determine the effects of GABA on chloride equilibrium, thereby determining whether GABA produces hyperpolarizing or depolarizing actions following activation of GABAA receptors. The activity of Na-K-2Cl cotransporter1 (NKCC1), the most prevalent chloride influx cotransporter isoform in the brain, plays a critical role in determining whether GABA has depolarizing effects. In the present study, we tested the hypothesis that NKCC1 protein expression in the SCN is regulated by environmental lighting and displays daily and circadian changes in the intact circadian system of the Syrian hamster. In hamsters housed in constant light (LL), the overall NKCC1 immunoreactivity (NKCC1-ir) in the SCN was significantly greater than in hamsters housed in LD or constant darkness (DD), although NKCC1 protein levels in the SCN were not different between hamsters housed in LD and DD. In hamsters housed in LD cycles, no differences in NKCC1-ir within the SCN were observed over the 24-h cycle. NKCC1 protein in the SCN was found to vary significantly over the circadian cycle in hamsters housed in free-running conditions. Overall, NKCC1 protein was greater in the ventral SCN than in the dorsal SCN, although no significant differences were observed across lighting conditions or time of day in either subregion. These data support the hypothesis that NKCC1 protein expression can be regulated by environmental lighting and circadian mechanisms within the SCN.

中文翻译:

GABA在视交叉上核内的兴奋作用:通过环境光照条件调节Na-K-2Cl共转运蛋白(NKCC)。

视交叉上核(SCN)包含一个起搏器,可产生昼夜节律并将其带入24小时的明暗循环(LD)。SCN由双侧配对核中的16,000至20,000个异质神经元组成。γ-氨基丁酸(GABA)是SCN中的主要神经化学信号,在调节昼夜节律功能中起关键作用。尽管GABA是大脑中主要的抑制性神经递质,但现在有证据表明GABA也可以在成年大脑中发挥兴奋作用。阳离子氯化物共转运蛋白决定了GABA对氯化物平衡的影响,从而确定了GABA在激活GABAA受体后是否产生超极化或去极化作用。Na-K-2Cl cotransporter1(NKCC1)是大脑中最普遍的氯离子流入cotransporter亚型的活性,在确定GABA是否具有去极化作用方面起着至关重要的作用。在本研究中,我们测试了SCN中NKCC1蛋白表达受环境光照调节并在叙利亚仓鼠完整昼夜节律系统中显示每日和昼夜节律变化的假设。在恒定光照(LL)的仓鼠中,尽管SCN中NKCC1的蛋白质水平没有差异,但SCN中的整体NKCC1免疫反应性(NKCC1-ir)明显大于LD或恒定黑暗(DD)的仓鼠。分别位于LD和DD。在LD周期的仓鼠中,在24小时的周期内,SCN内的NKCC1-ir没有差异。发现在自由运行条件下饲养的仓鼠中,SCN中的NKCC1蛋白在昼夜节律周期中有显着变化。总体,腹侧SCN中的NKCC1蛋白比背侧SCN中的更大,尽管在任何一个分区的光照条件或一天中的不同时段都没有观察到显着差异。这些数据支持这样的假设,即NKCC1蛋白表达可以受SCN中的环境照明和昼夜节律机制调节。
更新日期:2020-05-14
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