Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Dorothy Hodgkin Building, School of Clinical Sciences, University of Bristol, BS1 3NY, UK.
School of Physiology and Pharmacology, University of Bristol, Medical Sciences Building, University Walk, BS8 1TD, UK.
Exp Neurol. 2014 Jun;256:93-104. doi: 10.1016/j.expneurol.2014.04.001. Epub 2014 Apr 12.
Galanin is a pleiotropic neuropeptide widely expressed in the nervous system. It plays a role in many diverse physiological functions - including nociception, cognition and metabolism regulation - and acts as neurotrophic/neuroprotective factor for several neuronal populations. In this article we sought to determine the role of galanin on neural stem cell function and its contribution to the plasticity of the nervous system. Here we show that galanin and its receptors are expressed in neural progenitor cells (NPCs) isolated from the developing striatum. Stimulation with galanin results in upregulation of Bcl-Xl, Bcl-2, Mash-1 and Olig-2 that are part of well known pro-survival/pro-neuronal signalling pathways. Accordingly, treatment with galanin increases the number of neurons upon differentiation from these progenitors. We then show that these effects are recapitulated in NPCs isolated from the adult subventricular zone (SVZ), where galanin increases the total number of neurons and the number of newly-generated neurons upon differentiation in vitro. The significance of these findings is highlighted in the adult brain where loss of galanin leads to a marked decrease in the rate of adult SVZ neurogenesis and a reduction in the number of newly generated cells in the olfactory bulb. Interestingly, Gal-KO mice display normal performances in simple tasks of olfactory detection and discrimination, which points to the existence of a certain degree of redundancy in SVZ neurogenesis. Our findings establish the role of galanin as a modulator of neural stem cell function and support the importance of galanin for brain plasticity and repair.
甘丙肽是一种广泛表达于神经系统的多功能神经肽。它在许多不同的生理功能中发挥作用——包括痛觉、认知和代谢调节——并作为多种神经元群体的神经营养/神经保护因子。在本文中，我们试图确定甘丙肽对神经干细胞功能的作用及其对神经系统可塑性的贡献。在这里，我们表明甘丙肽及其受体存在于从发育中的纹状体分离的神经祖细胞（NPC）中。甘丙肽刺激导致 Bcl-Xl、Bcl-2、Mash-1 和 Olig-2 的上调，这些都是众所周知的促生存/促神经元信号通路的一部分。因此，用甘丙肽处理可增加这些祖细胞分化为神经元的数量。然后，我们表明这些效应在从成年侧脑室下区（SVZ）分离的 NPC 中得到重现，其中甘丙肽在体外分化时增加神经元的总数和新生成神经元的数量。这些发现的意义在成年大脑中得到了强调，在成年 SVZ 神经发生中，甘丙肽的缺失导致神经发生率明显下降，嗅球中新生成的细胞数量减少。有趣的是，Gal-KO 小鼠在简单的嗅觉检测和辨别任务中表现正常，这表明 SVZ 神经发生存在一定程度的冗余。我们的研究结果确立了甘丙肽作为神经干细胞功能调节剂的作用，并支持甘丙肽对大脑可塑性和修复的重要性。
