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小鼠成体神经干细胞的激活受昼夜周期和细胞内钙动力学的调节
作者:小柯机器人 发布时间:2021/1/24 20:23:44

加拿大拉瓦尔大学Armen Saghatelyan小组发现,小鼠成体神经干细胞的激活受昼夜周期和细胞内钙动力学的调节。这一研究成果于2021年1月21日在线发表在国际学术期刊《细胞》上。

研究人员定制了一套体内成像方案,可以跟踪神经干细胞(NSC)数天至几个月,并观察其在行为自由小鼠中的激活动力学。令人惊讶的是,NSC分裂在白天更为频繁,并受到黑暗诱导的褪黑激素信号抑制。褪黑激素受体的抑制影响细胞内Ca2+动力学并促进NSC激活。

研究人员进一步发现了静态和激活的NSC的Ca2+标记,并显示了几种微环境信号在细胞内Ca2+途径上会聚,进而调节NSC的静态和激活。体内NSC特异性Ca2+流的光遗传学调节能够模仿自由行为小鼠中的静止状态样Ca2+动力学,从而阻断了NSC激活并保持了其静止状态。

这些发现揭示了介导自由行为动物中NSC激活的调节机制。

据介绍,成年大脑中的NSC从静止状态过渡到增殖来产生新的神经元。然而,人们对行动自由的动物中调节这种转变的机制了解甚少。

附:英文原文

Title: Adult neural stem cell activation in mice is regulated by the day/night cycle and intracellular calcium dynamics

Author: Archana Gengatharan, Sarah Malvaut, Alina Marymonchyk, Majid Ghareghani, Marina Snapyan, Judith Fischer-Sternjak, Jovica Ninkovic, Magdalena Gtz, Armen Saghatelyan

Issue&Volume: 2021-01-21

Abstract: Neural stem cells (NSCs) in the adult brain transit from the quiescent state to proliferationto produce new neurons. The mechanisms regulating this transition in freely behavinganimals are, however, poorly understood. We customized in vivo imaging protocols to follow NSCs for several days up to months, observing their activationkinetics in freely behaving mice. Strikingly, NSC division is more frequent duringdaylight and is inhibited by darkness-induced melatonin signaling. The inhibitionof melatonin receptors affected intracellular Ca2+ dynamics and promoted NSC activation. We further discovered a Ca2+ signature of quiescent versus activated NSCs and showed that several microenvironmentalsignals converge on intracellular Ca2+ pathways to regulate NSC quiescence and activation. In vivo NSC-specific optogenetic modulation of Ca2+ fluxes to mimic quiescent-state-like Ca2+ dynamics in freely behaving mice blocked NSC activation and maintained their quiescence,pointing to the regulatory mechanisms mediating NSC activation in freely behavinganimals.

DOI: 10.1016/j.cell.2020.12.026

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31748-7

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/