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生长激素释放肽促进中脑神经干细胞通过 Wnt/β-连环蛋白通路向多巴胺能神经元分化。

Ghrelin promotes midbrain neural stem cells differentiation to dopaminergic neurons through Wnt/β-catenin pathway.

机构信息

Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, School of Basic Medicine, Qingdao University, Qingdao, China.

出版信息

J Cell Physiol. 2020 Nov;235(11):8558-8570. doi: 10.1002/jcp.29699. Epub 2020 Apr 24.

Abstract

Ghrelin plays a neuroprotective role in the process of dopaminergic (DAergic) neurons degeneration in Parkinson's disease (PD). However, it still largely unknown whether ghrelin could affect the midbrain neural stem cells (mbNSCs) from which DAergic neurons are originated. In the present study, we observed that ghrelin enhanced mbNSCs proliferation, and promoted neuronal differentiation especially DAergic neuron differentiation both in vitro and ex vivo. The messenger RNA levels of Wnt1, Wnt3a, and glial cell line-derived neurotrophic factor were increased in response to the ghrelin treatment. Results showed that Wnt/β-catenin pathway was relevant to this DAergic neuron differentiation induced by ghrelin. Our finding gave a new evidence that ghrelin may enable clinical therapies for PD by its neurogenesis role.

摘要

胃饥饿素在帕金森病(PD)中多巴胺能(DAergic)神经元变性过程中发挥神经保护作用。然而,胃饥饿素是否能影响从中分化出 DAergic 神经元的中脑神经干细胞(mbNSCs),这在很大程度上仍不清楚。在本研究中,我们观察到胃饥饿素在体外和体内均增强 mbNSCs 的增殖,并促进神经元分化,特别是 DAergic 神经元分化。ghrelin 处理后,Wnt1、Wnt3a 和胶质细胞源性神经营养因子的信使 RNA 水平增加。结果表明,Wnt/β-catenin 通路与 ghrelin 诱导的这种 DAergic 神经元分化有关。我们的发现为胃饥饿素通过其神经发生作用可能为 PD 的临床治疗提供了新的证据。

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