title: The extracellular matrix in plasticity and regeneration after CNS injury and neurodegenerative disease.
abstract: Chondroitin sulfate proteoglycans (CSPGs) are involved in several processes relevant to recovery of function after CNS damage. They restrict axon regeneration through their presence in glial scar tissue and plasticity through their presence in perineuronal nets (PNNs), affect memory through their effect on dendritic spines, and influence the inflammatory reaction. Much of our knowledge of these CSPG effects comes from digestion of their glycosaminoglycan chains by the enzyme chondroitinase ABC (ChABC). ChABC after spinal cord injury permits some axon regeneration and greatly increases plasticity through increased sprouting and through digestion of PNNs. When combined with appropriate rehabilitation, ChABC treatment can lead to considerable restoration of function. ChABC treatment of the perirhinal cortex greatly increases retention of object recognition memory. When applied to tauopathy animals that model Alzheimer's disease, ChABC digestion can restore normal object recognition memory. CSPGs in the adult CNS are found throughout the ECM, but 2% is concentrated in PNNs that surround GABAergic parvalbumin interneurons and other neurons. Knockout of the PNN-organizing protein Crtl1 link protein attenuates PNNs and leads to continued plasticity into adulthood, demonstrating that the CSPGs in PNNs are the key components in the control of plasticity. CSPGs act mainly through their sulfated glycosaminoglycan chains. A disulfated CS-E motif in these chains is responsible for binding of Semaphorin 3A to PNNs where it affects ocular dominance plasticity and probably other forms of plasticity. In addition OTX2 binds to CS-E motifs, where it can act on parvalbumin interneurons to maintain the PNNs.
authors.affiliation: Department of Clinical Neuroscience, John van Geest Centre for Brain Repair, University of Cambridge, Robinson Way, CA, UK. Electronic address: jf108@cam.ac.uk.
authors.forename: James W
authors.initials: JW
authors.lastname: Fawcett
mesh_terms: D000818:Animals; D002493:Central Nervous System Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*
keywords: Semaphorin; axon regeneration; chondroitin sulfate proteoglycan; chondroitinase; extracellular matrix; ocular dominance; plasticity; proteoglycan; spinal cord