Identification and regulation of neural stem cells in the adult mammalian hypothalamus

成年哺乳动物下丘脑神经干细胞的鉴定和调控

• 批准号: 218641401
• 负责人: Dr. Hai-Kun Liu, Ph.D.
• 金额: --
• 依托单位: Abteilung Molekulare Neurogenetik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/218641401?language=en
• 关键词: Identification; regulation; neural; stem; cells

Adult mammalian neural stem cells (NSCs) provide striking evidence of plasticity of the central nervous system and open up a new possibility for cell replacement therapy for neurological disorders. No solid evidence has been demonstrated for the existence of NSCs in the adult hypothalamus, which is an essential region for many important behaviors that are essential for survival. This proposal aims to identify a novel neural stem cell population in the adult mammalian hypothalamus. We found that in the adult mouse hypothalamus there is a small population of cells, which expresses the nuclear receptor protein Tlx and can give rise to new neurons when exposed to growth factors in vivo. This strongly suggests that the Tlx expressing cells are the origin of new neurons in the adult hypothalamus. We will first analyze the microenvironment of these Tlx expressing cells and their potential to generate different neuronal subtypes will be investigated using the established animal models. As a NSCs determinant in the adult mouse brain, the role of Tlx will be further analyzed using gain or loss-off function. Changes and contribution of the hypothalamic NSCs during aging and brain injury will be investigated. The results and genetic tools obtained from the proposed projects will settle the basis for studying the adult hypothalamic NSCs in vivo, which will greatly increase the feasibility to investigate the significance of hypothalamic adult neurogenesis. Thus provide new insights in understanding many diseases which are related to hypothalamus dysregulation, such as obesity and aggression.

成年哺乳动物神经干细胞（NSCs）提供了中枢神经系统可塑性的显著证据，并为神经系统疾病的细胞替代治疗开辟了新的可能性。成年人下丘脑是许多重要行为的重要区域，对生存至关重要，但没有确凿的证据表明下丘脑中存在神经干细胞。该建议旨在确定一种新的神经干细胞群在成年哺乳动物下丘脑。我们发现，在成年小鼠下丘脑有一小群细胞，表达核受体蛋白Tlx，并能产生新的神经元时，暴露于生长因子在体内。这有力地表明，Tlx表达细胞是成人下丘脑中新神经元的起源。我们将首先分析这些Tlx表达细胞的微环境，并使用已建立的动物模型研究它们产生不同神经元亚型的潜力。作为成年小鼠脑中的NSC决定因子，Tlx的作用将使用增益或损失函数进一步分析。本研究将探讨下丘脑神经干细胞在衰老和脑损伤过程中的变化和作用。本课题的研究结果和遗传学工具将为在体研究成体下丘脑神经干细胞奠定基础，为进一步研究成体下丘脑神经发生的意义提供可行性。从而为认识肥胖、攻击性等与下丘脑功能失调有关的疾病提供了新的思路。