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以及——出生后下丘脑神经发生的新型调控因子。

and - Novel Regulatory Factors of Postnatal Hypothalamic Neurogenesis.

作者信息

Dou Zhengchao, Son Joe Eun, Hui Chi-Chung

机构信息

Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada.

Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.

出版信息

Front Neurosci. 2021 Nov 2;15:763856. doi: 10.3389/fnins.2021.763856. eCollection 2021.

Abstract

The hypothalamus is a brain region that exhibits highly conserved anatomy across vertebrate species and functions as a central regulatory hub for many physiological processes such as energy homeostasis and circadian rhythm. Neurons in the arcuate nucleus of the hypothalamus are largely responsible for sensing of peripheral signals such as leptin and insulin, and are critical for the regulation of food intake and energy expenditure. While these neurons are mainly born during embryogenesis, accumulating evidence have demonstrated that neurogenesis also occurs in postnatal-adult mouse hypothalamus, particularly in the first two postnatal weeks. This second wave of active neurogenesis contributes to the remodeling of hypothalamic neuronal populations and regulation of energy homeostasis including hypothalamic leptin sensing. Radial glia cell types, such as tanycytes, are known to act as neuronal progenitors in the postnatal mouse hypothalamus. Our recent study unveiled a previously unreported radial glia-like neural stem cell (RGL-NSC) population that actively contributes to neurogenesis in the postnatal mouse hypothalamus. We also identified and , which encode homeodomain-containing transcription factors, as genetic determinants regulating the neurogenic property of these RGL-NSCs. These findings are significant as and have been implicated in -associated obesity in humans, illustrating the importance of postnatal hypothalamic neurogenesis in energy homeostasis and obesity. In this review, we summarize current knowledge regarding postnatal-adult hypothalamic neurogenesis and highlight recent findings on the radial glia-like cells that contribute to the remodeling of postnatal mouse hypothalamus. We will discuss characteristics of the RGL-NSCs and potential actions of and in the regulation of neural stem cells in the postnatal-adult mouse brain. Understanding the behavior and regulation of neural stem cells in the postnatal-adult hypothalamus will provide novel mechanistic insights in the control of hypothalamic remodeling and energy homeostasis.

摘要

下丘脑是一个在脊椎动物物种中具有高度保守解剖结构的脑区,作为许多生理过程(如能量稳态和昼夜节律)的中央调节枢纽发挥作用。下丘脑弓状核中的神经元在很大程度上负责感知瘦素和胰岛素等外周信号,对食物摄入和能量消耗的调节至关重要。虽然这些神经元主要在胚胎发育期间产生,但越来越多的证据表明,神经发生也发生在出生后至成年小鼠的下丘脑,特别是在出生后的前两周。这第二轮活跃的神经发生有助于下丘脑神经元群体的重塑以及能量稳态的调节,包括下丘脑对瘦素的感知。放射状胶质细胞类型,如伸长细胞,已知在出生后小鼠下丘脑中充当神经元祖细胞。我们最近的研究发现了一种以前未报道过的放射状胶质样神经干细胞(RGL-NSC)群体,该群体积极参与出生后小鼠下丘脑的神经发生。我们还鉴定了 和 ,它们编码含同源结构域的转录因子,作为调节这些RGL-NSC神经发生特性的遗传决定因素。这些发现具有重要意义,因为 和 与人类的 相关肥胖有关,说明了出生后下丘脑神经发生在能量稳态和肥胖中的重要性。在这篇综述中,我们总结了关于出生后至成年下丘脑神经发生的当前知识,并强调了关于有助于出生后小鼠下丘脑重塑的放射状胶质样细胞的最新发现。我们将讨论RGL-NSC的特征以及 和 在出生后至成年小鼠大脑神经干细胞调节中的潜在作用。了解出生后至成年下丘脑神经干细胞的行为和调节将为下丘脑重塑和能量稳态的控制提供新的机制见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62a7/8593166/a9e5f62c6c96/fnins-15-763856-g001.jpg

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