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MiR-181a-5p promotes neural stem cell proliferation and enhances the learning and memory of aged mice.

ABSTRACT: Hippocampal neural stem cell (NSC) proliferation is known to decline with age, which is closely linked to learning and memory impairments. In the current study, we found that the expression level of miR-181a-5p was decreased in the hippocampal NSCs of aged mice and that exogenous overexpression of miR-181a-5p promoted NSC proliferation without affecting NSC differentiation into neurons and astrocytes. The mechanistic study revealed that phosphatase and tensin homolog (PTEN), a negative regulator of the AKT signaling pathway, was the target of miR-181a-5p and knockdown of PTEN could rescue the impairment of NSC proliferation caused by low miR-181a-5p levels. Moreover, overexpression of miR-181a-5p in the dentate gyrus enhanced the proliferation of NSCs and ameliorated learning and memory impairments in aged mice. Taken together, our findings indicated that miR-181a-5p played a functional role in NSC proliferation and aging-related, hippocampus-dependent learning and memory impairments.

SUBMITTER: Sun Q

PROVIDER: S-EPMC10086527 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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MiR-181a-5p promotes neural stem cell proliferation and enhances the learning and memory of aged mice.

Sun Qiaoyi Q Ma Li L Qiao Jing J Wang Xing X Li Jianguo J Wang Yuxi Y Tan Ailing A Ye Zihui Z Wu Yukang Y Xi Jiajie J Kang Jiuhong J

Aging cell 20230216 4

Hippocampal neural stem cell (NSC) proliferation is known to decline with age, which is closely linked to learning and memory impairments. In the current study, we found that the expression level of miR-181a-5p was decreased in the hippocampal NSCs of aged mice and that exogenous overexpression of miR-181a-5p promoted NSC proliferation without affecting NSC differentiation into neurons and astrocytes. The mechanistic study revealed that phosphatase and tensin homolog (PTEN), a negative regulator ...[more]

PMID: 36797653

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Project description:Diabetic nephropathy (DN) is a chronic loss of kidney function that frequently occurs in patients with diabetes mellitus and is characterized by abnormal glomerular mesangial cell (GMC) proliferation and apoptosis. By using microarray analysis, microRNA (miR)-181a-5p has previously been identified to be dysregulated in DN. The present study aimed to determine the underlying molecular mechanisms and function of miR-181a-5p in GMCs under DN conditions. First, reverse transcription-quantitative PCR was performed to detect miR-181a-5p and kruppel-like factor 6 (KLF6) expression in GMCs following high-glucose treatment. Subsequently, MTT and flow cytometric assays were performed in order to determine the effect of miR-181a-5p and KLF6 on high-glucose-driven GMC proliferation and apoptosis. After confirming that KLF6 was a target gene of miR-181a-5p via a bioinformatics analysis and luciferase reporter assay, the mRNA and protein expression levels of associated factors in different treatment groups were measured. The results demonstrated that miR-181a-5p was significantly downregulated, while KLF6 was significantly upregulated in GMCs following treatment with high glucose. Furthermore, overexpression of miR-181a led to suppression of cell proliferation and promoted apoptosis of GMCs induced by high glucose, while these effects were inhibited by co-transfection with KLF6. Finally, miR-181-5p was demonstrated to inhibit the expression of KLF6, Bcl-2, Wnt1 and β-catenin, while increasing the expression levels of Bax and caspase-3. In conclusion, the expression levels of miR-181a-5p were downregulated in GMCs following treatment with high glucose and overexpression of miR-181a-5p may inhibit GMC proliferation and promote apoptosis, at least partially through targeting KLF6 via the Wnt/β-catenin signaling pathway. Overall, the results of the present study suggest that miR-181a-5p may have a crucial role in the occurrence and development of DN and may be a valuable diagnostic marker and therapeutic target for DN.

Dataset Information

MiR-181a-5p promotes neural stem cell proliferation and enhances the learning and memory of aged mice.

Publications

MiR-181a-5p promotes neural stem cell proliferation and enhances the learning and memory of aged mice.

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