Distinct roles for hyaluronan in neural stem cell niches and perineuronal nets

Adult neurogenesis in mammals is a tightly regulated process where neural stem cells (NSCs), especially in the subgranular zone (SGZ) of the hippocampal dentate gyrus, proliferate and differentiate into new neurons that form new circuits or integrate into old circuits involved in episodic memory, pattern discrimination, and emotional responses. Recent evidence suggests that changes in the hyaluronan (HA)-based extracellular matrix of the SGZ may regulate neurogenesis by controlling NSC proliferation and early steps in neuronal differentiation. These studies raise the intriguing possibility that perturbations in this matrix, including HA accumulation with aging, could impact adult neurogenesis and cognitive functions, and that alterations to this matrix could be beneficial following insults to the central nervous system that impact hippocampal functions.