miR-132 couples the circadian clock to daily rhythms of neuronal plasticity and cognition.
miR-132 couples the circadian clock to daily rhythms of neuronal plasticity and cognition.
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DOI：
10.1101/lm.047191.117
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Obrietan K
中科院分区：
文献类型：
--
作者：
Aten S;Hansen KF;Price KH;Wheaton K;Kalidindi A;Garcia A;Alzate-Correa D;Hoyt KR;Obrietan K
microRNA miR-132在中枢神经系统中广泛的可塑性相关过程中起关键调节作用。有趣的是，miR-132的表达也受到昼夜节律系统的控制。这一发现，再加上研究表明miR-132在海马体中表达，在海马体中影响神经元形态和记忆，使我们验证了前脑内miR-132的日常节律作为昼夜节律时间的函数调节认知的观点。在这里，我们表明海马miR-132的表达是由一天中的时间控制的，峰值水平发生在昼夜节律的夜晚。此外，在miR-132敲除小鼠和转基因小鼠中，miR-132在四环素调节系统的控制下组成性表达，我们发现每天依赖的记忆回忆（通过新物体定位和情境恐惧条件反射范式评估）被抑制。鉴于mirna通过抑制靶基因表达来发挥其功能作用，我们研究了转基因miR-132操作对MeCP2和sirt1这两个与神经元可塑性和认知相关的miR-132靶点的影响。在敲除或转基因表达miR-132的小鼠中，MeCP2和Sirt1的节律性表达被抑制。综上所述，这些结果提出了miR-132作为昼夜节律系统赋予认知能力日常节律的关键途径的前景。
The microRNA miR-132 serves as a key regulator of a wide range of plasticity-associated processes in the central nervous system. Interestingly, miR-132 expression has also been shown to be under the control of the circadian timing system. This finding, coupled with work showing that miR-132 is expressed in the hippocampus, where it influences neuronal morphology and memory, led us to test the idea that daily rhythms in miR-132 within the forebrain modulate cognition as a function of circadian time. Here, we show that hippocampal miR-132 expression is gated by the time-of-day, with peak levels occurring during the circadian night. Further, in miR-132 knockout mice and in transgenic mice, where miR-132 is constitutively expressed under the control of the tetracycline regulator system, we found that time-of-day dependent memory recall (as assessed via novel object location and contextual fear conditioning paradigms) was suppressed. Given that miRNAs exert their functional effects via the suppression of target gene expression, we examined the effects that transgenic miR-132 manipulations have on MeCP2 and Sirt1—two miR-132 targets that are associated with neuronal plasticity and cognition. In mice where miR-132 was either knocked out, or transgenically expressed, rhythmic expression of MeCP2 and Sirt1 was suppressed. Taken together, these results raise the prospect that miR-132 serves as a key route through which the circadian timing system imparts a daily rhythm on cognitive capacity.
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DOI：
10.1038/nrn2881
发表时间：
2010-08
期刊：
Nature reviews. Neuroscience
影响因子：
--
作者：
Gerstner JR;Yin JC
通讯作者：
Yin JC
影响因子：
16.2
作者：
Edbauer, Dieter;Neilson, Joel R.;Foster, Kelly A.;Wang, Chi-Fong;Seeburg, Daniel P.;Batterton, Matthew N.;Tada, Tomoko;Dolan, Bridget M.;Sharp, Phillip A.;Sheng, Morgan
通讯作者：
Sheng, Morgan
SIRT1 调节海马神经元树突状发育。
影响因子：
3.7
作者：
Codocedo JF;Allard C;Godoy JA;Varela-Nallar L;Inestrosa NC
通讯作者：
Inestrosa NC
影响因子：
2.7
作者：
Besheer, J;Jensen, HC;Bevins, RA
通讯作者：
Bevins, RA
影响因子：
2.8
作者：
Campos, Leila M. G.;Osorio, Elaine C.;Pinato, Luciana
通讯作者：
Pinato, Luciana