The Cell-Autonomous Role of Caveolin-1 in Adult Hippocampal Neurogenesis

The mechanisms governing adult hippocampal neurogenesis (AHN) remain incompletely understood, despite its crucial roles in learning and memory. Identifying the signals that regulate AHN has significant implications for brain function and therapeutic strategies. Here, we demonstrate that Caveolin-1 (Cav-1), a protein highly enriched in endothelial cells and a key component of caveolae, cell autonomously regulates AHN. Conditional deletion of Cav-1 in adult neural progenitor cells enhanced neurogenesis and improved contextual discrimination performance in mice. Proteomic analysis revealed that Cav-1 influences mitochondrial pathways in neural progenitor cells. Notably, Cav-1 localized to mitochondria and regulated mitochondrial morphology, an outcome of fission-fusion dynamics—a critical process in neurogenesis. These findings identify Cav-1 as a novel regulator of AHN and underscore its impact on cognitive function.