Restoring carboxypeptidase E rescues BDNF maturation and neurogenesis in aged brains.

ABSTRACT: Adult neurogenesis declines with age due to the less functional neural stem cells (NSCs) and niches, but the underlying molecular bases for this impaired condition remain unclear. Here we analyzed >55,000 single-cell transcriptomes from two discrete neurogenic niches across the mouse lifespan, and identified new features and populations in NSCs, new markers, and neurogenic regional-specific alternations during aging. Intercellular communication analysis revealed defects in brain-derived neurotrophic factor (BDNF)-TrkB signaling cascade in old NSCs. Carboxypeptidase E (CPE) was found to be highly enriched in NSCs, and played a crucial role in mature/proBDNF balance and adult neurogenesis. Diminishment of CPE with aging resulted in impaired generation of BDNF, thus limiting the neurogenesis

SUBMITTER: Liu H 

PROVIDER: S-EPMC11749474 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature