MicroRNA-153 improves the neurogenesis of neural stem cells and enhances the cognitive ability of aged mice through the notch signaling pathway

Abstract

Aging-related cognitive ability impairments are one of the main threats to public health, and impaired hippocampal neurogenesis is a major cause of cognitive decline during aging. However, the regulation of adult neurogenesis in the hippocampus requires further study. Here, we investigated the role of microRNA-153 (miR-153), a highly conserved microRNA in mice and humans, in adult neurogenesis. During the passaging of neural stem cells (NSCs) in vitro, endogenous miR-153 expression was downregulated, with a decrease in neuronal differentiation ability. In addition, miR-153 overexpression increased the neurogenesis of NSCs. Further studies showed that miR-153 regulated neurogenesis by precisely targeting the Notch signaling pathway through inhibition of Jagged1 and Hey2 translation. In vivo analysis demonstrated that miR-153 expression was decreased in the hippocampi of aged mice with impaired cognitive ability, and that miR-153 overexpression in the hippocampus promoted neurogenesis and markedly increased the cognitive abilities of the aged mice. Overall, our findings revealed that miR-153 affected neurogenesis by regulating the Notch signaling pathway and elucidated the function of miR-153 in aging-related, hippocampus-dependent cognitive ability impairments, and neurodegenerative diseases.

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Data availability

The additional data or reagents are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported by the Ministry of Science and Technology (grant 2016YFA0101300), the National Natural Science Foundation of China (grants 81530042, 31721003, 31871495, 31571529, 31571519, 31701110, and 31671533), and Shanghai Municipal Medical and Health Discipline Construction Projects (grant 2017ZZ02015).

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The author contributions can be found in the Supplementary Material. All authors read and approved the final paper.

Correspondence to Jiajie Xi or Jiuhong Kang.

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