COL6A3 regulates adult neurogenesis in the hippocampus by modulating cellular senescence within the neural stem cell niche

Abstract

In the adult mammalian hippocampus, new neurons arise from neural stem and progenitor cells, a process known as adult neurogenesis. Adult neurogenesis plays a vital role in cognitive functions like learning and memory. Recent studies suggest that extracellular matrix (ECM) molecules are involved in the process of adult neurogenesis. In our research, we have identified Collagen Type VI Alpha 3 Chain (COL6A3) as a regulator of adult neurogenesis in the hippocampus. In COL6A3-deficient mice, we observed a significant increase in neuronal development within the dentate gyrus (DG) region of the hippocampus and senescence markers in neural stem cells of the same region were reduced. Additionally, COL6A3-deficient mice exhibited enhanced learning and memory abilities that rely on the hippocampus. Our results confirm that COL6A3 is a regulator of adult neurogenesis in the hippocampus by modulating the cellular senescence of neural stem cells. This suggests its potential as a therapeutic target for neurodegenerative diseases such as Alzheimer's disease (AD)