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中脑三叉神经核培养物中昼夜节律性mPer1基因表达

Circadian mPer1 gene expression in mesencephalic trigeminal nucleus cultures.

作者信息

Hiler Daniel J, Bhattacherjee Aritra, Yamazaki Shin, Tei Hajime, Geusz Michael E

机构信息

Department of Biological Sciences and the J.P. Scott Center for Neuroscience, Mind, and Behavior, Bowling Green State University, Bowling Green, OH 43403-0208, USA.

出版信息

Brain Res. 2008 Jun 12;1214:84-93. doi: 10.1016/j.brainres.2008.03.041. Epub 2008 Apr 1.

Abstract

The circadian timing system includes the major circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus and less well characterized circadian pacemakers in the brain and peripheral tissues throughout the body. The coupling between these discrete circadian clocks is not well understood, although individual neurons of the SCN are considered competent circadian pacemakers that interact to produce rhythms in the SCN and in its afferents. Because the SCN is a complex assemblage of small neurons of several phenotypes, we sought a simpler circadian brain nucleus with larger neurons that might provide insight into circadian timing not easily obtained from the SCN. Using bioluminescence imaging of brain tissue explants from transgenic mice containing the firefly luciferase gene luc controlled by the mPer1 promoter, we discovered elevated transgene expression throughout the mesencephalic trigeminal nucleus (Me5) of the brain stem. Large sensory neurons of the Me5 receive proprioceptive signals from periodontal ligaments and masseter muscle spindles. The Me5 cells displayed circadian rhythms with elevated expression in culture corresponding with the dark portion of the prior light cycle. Because of known interactions between the Me5 and the tuberomammillary nucleus and because of the role of both nuclei in satiety, it is possible that a circadian clock in the Me5 serves in regulating daily feeding behavior. This newly identified circadian pacemaker in the Me5 may prove useful for single-cell analyses of circadian gene expression in clock cells and for comparison with the SCN.

摘要

昼夜节律计时系统包括下丘脑视交叉上核(SCN)中的主要昼夜节律起搏器以及分布于大脑和全身外周组织中特征尚不明确的昼夜节律起搏器。尽管SCN的单个神经元被认为是有功能的昼夜节律起搏器,它们相互作用以在SCN及其传入神经中产生节律,但这些离散的昼夜节律时钟之间的耦合尚未完全了解。由于SCN是由几种表型的小神经元组成的复杂集合体,我们寻找了一个更简单的昼夜节律脑核,其中含有较大的神经元,这可能有助于深入了解从SCN不易获得的昼夜节律计时机制。利用来自含有由mPer1启动子控制的萤火虫荧光素酶基因luc的转基因小鼠的脑组织外植体进行生物发光成像,我们发现脑干的中脑三叉神经核(Me5)中转基因表达升高。Me5的大型感觉神经元从牙周韧带和咬肌肌梭接收本体感觉信号。Me5细胞在培养物中显示出昼夜节律,其表达升高与先前光周期的黑暗部分相对应。由于已知Me5与结节乳头体核之间存在相互作用,并且由于这两个核在饱腹感中的作用,Me5中的昼夜节律时钟可能参与调节日常进食行为。这个新发现的Me5中的昼夜节律起搏器可能对时钟细胞中昼夜节律基因表达的单细胞分析以及与SCN的比较有用。

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