Rbm8a regulates neurogenesis and reduces Alzheimer’s disease-associated pathology in the dentate gyrus of 5×FAD mice

Author:

Zhu Chenlu1,Ren Xiao2,Liu Chen3,Liu Yawei4ORCID,Wang Yonggang15ORCID

Affiliation:

1. Department of Neurology, Lanzhou University Second Hospital, Lanzhou, Gansu Province, China

2. Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China

3. Department of Neurology, Xiaogan City Central Hospital, Xiaogan, Hubei Province, China

4. Health Service Department of the Guard Bureau of the General Office of the Central Committee of the Communist Party of China, Beijing, China

5. Headache Center, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Abstract

JOURNAL/nrgr/04.03/01300535-202404000-00031/inline-graphic1/v/2023-09-09T133047Z/r/image-tiff Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline, which can be partly attributed to impaired hippocampal neurogenesis. Neurogenesis in the hippocampal dentate gyrus is likely to persist throughout life but declines with aging, especially in Alzheimer’s disease. Recent evidence indicated that RNA-binding protein 8A (Rbm8a) promotes the proliferation of neural progenitor cells, with lower expression levels observed in Alzheimer’s disease patients compared with healthy people. This study investigated the hypothesis that Rbm8a overexpression may enhance neurogenesis by promoting the proliferation of neural progenitor cells to improve memory impairment in Alzheimer’s disease. Therefore, Rbm8a overexpression was induced in the dentate gyrus of 5×FAD mice to validate this hypothesis. Elevated Rbm8a levels in the dentate gyrus triggered neurogenesis and abated pathological phenotypes (such as plaque formation, gliosis reaction, and dystrophic neurites), leading to ameliorated memory performance in 5×FAD mice. RNA sequencing data further substantiated these findings, showing the enrichment of differentially expressed genes involved in biological processes including neurogenesis, cell proliferation, and amyloid protein formation. In conclusion, overexpressing Rbm8a in the dentate gyrus of 5×FAD mouse brains improved cognitive function by ameliorating amyloid-beta-associated pathological phenotypes and enhancing neurogenesis.

Publisher

Medknow

Subject

Developmental Neuroscience

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