Bressan Cedric, Saghatelyan Armen
CERVO Brain Research Center, Quebec City, QC, Canada.
Department of Psychiatry and Neuroscience, Université Laval, Quebec City, QC, Canada.
Front Cell Neurosci. 2021 Jan 13;14:620379. doi: 10.3389/fncel.2020.620379. eCollection 2020.
Neuronal migration is a fundamental brain development process that allows cells to move from their birthplaces to their sites of integration. Although neuronal migration largely ceases during embryonic and early postnatal development, neuroblasts continue to be produced and to migrate to a few regions of the adult brain such as the dentate gyrus and the subventricular zone (SVZ). In the SVZ, a large number of neuroblasts migrate into the olfactory bulb (OB) along the rostral migratory stream (RMS). Neuroblasts migrate in chains in a tightly organized micro-environment composed of astrocytes that ensheath the chains of neuroblasts and regulate their migration; the blood vessels that are used by neuroblasts as a physical scaffold and a source of molecular factors; and axons that modulate neuronal migration. In addition to diverse sets of extrinsic micro-environmental cues, long-distance neuronal migration involves a number of intrinsic mechanisms, including membrane and cytoskeleton remodeling, Ca signaling, mitochondria dynamics, energy consumption, and autophagy. All these mechanisms are required to cope with the different micro-environment signals and maintain cellular homeostasis in order to sustain the proper dynamics of migrating neuroblasts and their faithful arrival in the target regions. Neuroblasts in the postnatal brain not only migrate into the OB but may also deviate from their normal path to migrate to a site of injury induced by a stroke or by certain neurodegenerative disorders. In this review, we will focus on the intrinsic mechanisms that regulate long-distance neuroblast migration in the adult brain and on how these pathways may be modulated to control the recruitment of neuroblasts to damaged/diseased brain areas.
神经元迁移是大脑发育的一个基本过程,它使细胞能够从其诞生地移动到整合位点。虽然神经元迁移在胚胎期和出生后早期发育过程中基本停止,但神经母细胞仍会持续产生并迁移到成人大脑的一些区域,如齿状回和脑室下区(SVZ)。在脑室下区,大量神经母细胞沿着吻侧迁移流(RMS)迁移到嗅球(OB)。神经母细胞以链状形式在一个由星形胶质细胞构成的紧密组织化微环境中迁移,星形胶质细胞包裹着神经母细胞链并调节其迁移;神经母细胞将血管用作物理支架和分子因子来源;轴突则调节神经元迁移。除了各种外在的微环境线索外,长距离神经元迁移还涉及许多内在机制,包括膜和细胞骨架重塑、钙信号传导、线粒体动力学、能量消耗和自噬。所有这些机制都是应对不同微环境信号和维持细胞内稳态所必需的,以便维持迁移神经母细胞的正常动态及其准确到达目标区域。出生后大脑中的神经母细胞不仅迁移到嗅球,还可能偏离其正常路径迁移到中风或某些神经退行性疾病诱导的损伤部位。在这篇综述中,我们将重点关注调节成人大脑中长距离神经母细胞迁移的内在机制,以及如何调节这些途径以控制神经母细胞向受损/患病脑区的募集。