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使用抗抑郁药和间充质干细胞促进成年海马体中的神经发生。

Boosting Neurogenesis in the Adult Hippocampus Using Antidepressants and Mesenchymal Stem Cells.

机构信息

Department of Stem Cell Bioengineering, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawinskiego 5 Street, 02-106 Warsaw, Poland.

出版信息

Cells. 2022 Oct 14;11(20):3234. doi: 10.3390/cells11203234.

Abstract

The hippocampus is one of the few privileged regions (neural stem cell niche) of the brain, where neural stem cells differentiate into new neurons throughout adulthood. However, dysregulation of hippocampal neurogenesis with aging, injury, depression and neurodegenerative disease leads to debilitating cognitive impacts. These debilitating symptoms deteriorate the quality of life in the afflicted individuals. Impaired hippocampal neurogenesis is especially difficult to rescue with increasing age and neurodegeneration. However, the potential to boost endogenous Wnt signaling by influencing pathway modulators such as receptors, agonists, and antagonists through drug and cell therapy-based interventions offers hope. Restoration and augmentation of hampered Wnt signaling to facilitate increased hippocampal neurogenesis would serve as an endogenous repair mechanism and contribute to hippocampal structural and functional plasticity. This review focuses on the possible interaction between neurogenesis and Wnt signaling under the control of antidepressants and mesenchymal stem cells (MSCs) to overcome debilitating symptoms caused by age, diseases, or environmental factors such as stress. It will also address some current limitations hindering the direct extrapolation of research from animal models to human application, and the technical challenges associated with the MSCs and their cellular products as potential therapeutic solutions.

摘要

海马体是大脑中少数几个具有特权的区域(神经干细胞龛)之一,在整个成年期,神经干细胞分化为新的神经元。然而,随着年龄的增长、损伤、抑郁和神经退行性疾病,海马体神经发生的失调会导致使人衰弱的认知影响。这些使人衰弱的症状会降低患者的生活质量。随着年龄的增长和神经退行性疾病的加重,受损的海马体神经发生尤其难以恢复。然而,通过药物和细胞治疗干预,影响途径调节剂(如受体、激动剂和拮抗剂)来增强内源性 Wnt 信号的潜力带来了希望。恢复和增强受阻的 Wnt 信号以促进海马体神经发生将作为一种内源性修复机制,有助于海马体的结构和功能可塑性。本综述重点讨论了抗抑郁药和间充质干细胞(MSCs)控制下神经发生和 Wnt 信号之间的可能相互作用,以克服由年龄、疾病或环境因素(如压力)引起的使人衰弱的症状。它还将讨论一些当前的限制,这些限制阻碍了将动物模型的研究直接外推到人类应用,以及与 MSCs 及其细胞产物作为潜在治疗解决方案相关的技术挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cc0/9600461/175447725d1d/cells-11-03234-g001.jpg

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