Structural and Functional Remodeling of the Extracellular Matrix during Brain Development and Aging

The extracellular matrix (ECM) of the central nervous system (CNS) primarily consists of hyaluronan (HA) and chondroitin sulfate proteoglycans (CSPGs). HA polymer serves as the backbone of the ECM and binds multiple CSPGs, forming a macromolecular complex in the extracellular space. Recent advances in our understanding of the molecular mechanisms underlying the organization and remodeling of the ECM during the development, maturation, and aging of the CNS are reviewed herein. A juvenile-type ECM, which shows a relatively loose and diffuse structure, plays crucial roles in neural developmental processes, such as neurogenesis, neuronal migration, and neurite outgrowth. During late postnatal development, the juvenile-type ECM is replaced by an adult-type mature ECM, which drives the transition from more plastic, juvenile neural circuits to a more stable adult circuit. Perineuronal nets (PNNs), a prominent example of the adult-type ECM, are mesh-like insoluble aggregates that form around subpopulations of neurons and promote memory retention and consolidation in the adult brain. Furthermore, emerging evidence indicates that the degradation of ECM molecules during aging may contribute to an age-dependent decline in brain function.