The extracellular matrix in plasticity and regeneration after CNS injury and neurodegenerative disease

James W Fawcett
Progress in Brain Research 2015, 218: 213-26
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.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"