The extracellular matrix (ECM) plays a crucial role in maintaining brain homeostasis. Specifically, ECM serves as the neurogenic niche supporting the self-renewal and differentiation of neural stem cells (NSCs)/neuronal progenitor cells (NPCs) into newborn granule cells. One of the key components of the ECM structure is chondroitin sulfate proteoglycan (CSPG), consisting of a core protein and glycosaminoglycan side chains. CSPG has been implicated in embryonic neurogenesis and brain development. We have reported the potential of CSPG to promote the differentiation and maturation of NPCs in the adult mouse hippocampus. Another study highlighted the critical involvement of ECM composition in the differentiation and maturation of NSCs in the adult brain. Additionally, we reported that CSPG and newborn granule cells in the mouse hippocampus were increased by memantine, an anti-dementia drug. The expression levels of genes related to the biosynthesis and degradation of CSPG were increased and decreased by memantine, respectively. Anxiety-related behavior was reduced by memantine, short- and long-term memory performance were improved by memantine, and depletion of CSPG in the hippocampus impaired the effects of memantine. These findings suggest that ECM may be a potential therapeutic target for anti-dementia drugs.