Adult hippocampal neurogenesis (AHN) occurs throughout lifespan of humans and rodents and is correlated with memory performance and cognitive plasticity. In Alzheimer’s disease (AD), AHN is impeded, while the molecular basis behind this impairment remains to be elucidated. Here we identified Breast carcinoma amplified sequence 2 (BCAS2), a core component of the CDC5L/Prp19 spliceosome complex, regulating AHN in AD.
Using Bcas2 conditional knockout mice, AD mouse model APP/PS1 mice, established mouse primary adult neural stem cells and single cell sequencing, we demonstrate that BCAS2 replacement in adult mouse hippocampus promotes NSC activation and differentiation to neuron, restore AHN and relevant memory deficits through BDNF/TrkB signaling. Our findings corroborate the significance of AHN in AD and reveal the possible therapeutic potential of targeting BCAS2 in neurodegeneration. This is a preview of subscription content, access via your institution Receive 12 print issues and online access Prices may be subject to local taxes which are calculated during checkout All data supporting the findings of this study are available from the corresponding authors upon request.
The single-nucleus RNA sequencing and bulk RNA sequencing data supporting the findings of this study have been uploaded to the NCBI Gene Expression Omnibus (GEO) database and are available through the accession codes GSE331441 and GSE331130, respectively. All raw sequencing data are available under restricted access for the review process and will be made public upon publication. Kamatham PT, Shukla R, Khatri DK, Vora LK.
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