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Neural stem cell-derived exosomes improve neurite outgrowth and cognitive function through transferring miR-132-3p
Abstract
Background/aims Vascular dementia (VD) is accompanied by severe neuronal damage. Exosomal microRNAs (miRs) have been implicated in the neuroprotective effect of neural stem cells (NSCs), and miR-132-3p is a proneurogenic miR. In this study, we aimed to explore the role and underlying mechanisms of miR-132-3p-enriched NSC-EXs in VD-induced neuronal damage and synaptic impairment. Methods NSC-EXs, NSC-EXs enriched with miR-132-3p (NSC-EXs miR-132-3p ), and NSC-EXs deficient in miR-132-3p (NSC-EXs simiR-132-3p ) were cocultured with oxygen- and glucose-deprived (OGD)-injured neurons or administered to VD mice. Bioinformatic analyses and luciferase assays were used to determine the target genes of miR-132-3p. Results The levels of NSC-EXs and their associated miR-132-3p were markedly decreased in the hippocampi of VD mice. Compared with NSC-EXs, the infusion of NSC-EXs miR-132-3p was more effective at increasing the miR-132-3p level, neuron number, dendritic spine density and cognitive function and decreasing neuronal ROS production and apoptosis, whereas NSC-EXs simiR-132-3p treatment resulted in attenuated effects in comparison with those of NSC-EXs. In OGD-treated neurons, incubation with NSC-EXs miR-132-3p increased neurite outgrowth and decreased neuronal ROS production and apoptosis. Moreover, through bioinformatic analysis and cell transfection, we confirmed that NSC-EXs miR-132-3p promoted neurite outgrowth by targeting RASA1 and increasing the expression of downstream Ra…
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“Signaling through extracellular vesicles containing miR-132 from neurons to other cells has been shown to induce downstream effects [164–166], although elucidating the exact signaling mechanism in our experimental setup will require further research.”
From microRNA-132 attenuates inflammation in induced pluripotent stem cell-derived microglia from Alzheimer’s disease patients (2026) · cites this paper as [166]
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Cited by
Penning, A., Snoeck, S., Ormaechea, O. R., Ayyildiz, D., Polzer, O., Buitrago-Arango, M., Capobianco, R., de Winter, F., Balusu, S., Verhaagen, J., et al. (2026) · Acta Neuropathologica Communications · doi:10.1186/s40478-026-02228-8 · Cited by 6
Metadata
- Authors
- Wang, Y., Zhao, J., Guo, Q., Yin, Y., Tian, W., Wang, X., Deng, G., Pan, Q., & Ma, X.
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2025-06
- Volume
- 388
- Pages
- 115224
- ISSN
- 0014-4886
- Cited by
- 10
- References
- 40
- Language
- en
- Update notices
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Funders
- National Natural Science Foundation of China (82170407)
- Basic and Applied Basic Research Foundation of Guangdong Province (2022A1515012414)
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- Wang, Y., Zhao, J., Guo, Q., Yin, Y., Tian, W., Wang, X., Deng, G., Pan, Q., & Ma, X. (2025). Neural stem cell-derived exosomes improve neurite outgrowth and cognitive function through transferring miR-132-3p. Experimental Neurology. https://doi.org/10.1016/j.expneurol.2025.115224
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