miR-484 in Hippocampal Astrocytes of Aged and Young Rats Targets CSF-1 to Regulate Neural Progenitor/Stem Cell Proliferation and Differentiation Into Neurons

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2025-04-30 DOI:10.1111/cns.70415

Jiahua Qu, Zhichao Lu, Yongbo Cheng, Song Deng, Wei Shi, Qianqian Liu, Yuejuan Ling

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引用次数: 0

Abstract

Aim

Aging-related cognitive decline is closely linked to the reduced function of neural progenitor/stem cells (NPSCs), which can be influenced by the neural microenvironment, particularly astrocytes. The aim of this study was to explore how astrocytes affect NPSCs and cognitive function during aging.

Methods

H₂O₂-treated astrocytes were used to mimic the aging phenotype of astrocytes. Proteomic analysis identified altered protein expression, revealing high levels of colony-stimulating factor-1 (CSF-1) in the supernatant of H₂O₂-treated astrocytes. Primary NPSCs were isolated and cultured in vitro, then stimulated with varying concentrations of recombinant CSF-1 protein to assess its effects on NPSC proliferation, differentiation, and apoptosis. Transcriptome sequencing identified miR-484 related to CSF-1 in H₂O₂-treated astrocytes, and a dual-luciferase assay verified the interaction between miR-484 and CSF-1. The impact of miR-484 overexpression on NPSC function and cognitive restoration was evaluated both in vitro and in vivo (in 20-month-old rats).

Results

High concentration of CSF-1 inhibited the NPSC proliferation and differentiation into neurons while inducing apoptosis. Overexpression of miR-484 downregulated CSF-1 expression by binding to its 3' untranslated region, thereby promoting the NPSC proliferation and differentiation into neurons. In 20-month-old rats, miR-484 overexpression improved spatial learning and memory in the Morris water maze, increased NPSC proliferation, and reduced apoptosis.

Conclusion

Our findings reveal that miR-484 regulates CSF-1 to influence NPSC proliferation, differentiation into neurons, and apoptosis, consequently improving cognitive function in 20-month-old rats. This study provides a foundation for developing therapeutic strategies targeting age-related hippocampal cognitive impairments.

Abstract Image

查看原文本刊更多论文

老年和青年大鼠海马星形胶质细胞中的miR-484靶向CSF-1调节神经祖细胞/干细胞增殖和向神经元分化

目的与衰老相关的认知能力下降与神经祖细胞/干细胞（NPSCs）功能下降密切相关，神经祖细胞/干细胞（NPSCs）功能下降可受到神经微环境，特别是星形胶质细胞的影响。本研究旨在探讨星形胶质细胞在衰老过程中对npsc和认知功能的影响。方法采用h2o2处理的星形胶质细胞模拟星形胶质细胞的衰老表型。蛋白质组学分析发现，在h2o2处理的星形胶质细胞上清液中，蛋白质表达发生了改变，显示出高水平的集落刺激因子-1 （CSF-1）。我们分离并体外培养原代NPSC，然后用不同浓度的重组CSF-1蛋白刺激NPSC，以评估其对NPSC增殖、分化和凋亡的影响。转录组测序在h2o2处理的星形胶质细胞中鉴定出miR-484与CSF-1相关，双荧光素酶测定证实了miR-484与CSF-1之间的相互作用。在体外和体内（20月龄大鼠）评估miR-484过表达对NPSC功能和认知恢复的影响。结果高浓度CSF-1抑制NPSC向神经元的增殖和分化，同时诱导细胞凋亡。过表达miR-484通过结合其3'非翻译区下调CSF-1的表达，从而促进NPSC的增殖和向神经元分化。在20月龄大鼠中，miR-484过表达改善Morris水迷宫中的空间学习和记忆，增加NPSC增殖，减少凋亡。结论miR-484调节CSF-1影响20月龄大鼠NPSC的增殖、神经元分化和凋亡，从而改善其认知功能。本研究为开发针对年龄相关海马认知障碍的治疗策略提供了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.