Integrity of cortical perineuronal nets influences corticospinal tract plasticity after spinal cord injury.
The rapid decline of injury-induced neuronal circuit remodelling after birth is paralleled by the accumulation of chondroitin sulphate proteoglycans (CSPGs) in the extracellular matrix, culminating with the appearance of perineuronal nets (PNNs) around parvalbumin-expressing GABAergic interneurons. We used a spinal cord injury (SCI) model to study the interplay between integrity of PNN CSPGs in the sensorimotor cortex, anatomical remodelling of the corticospinal tract (CST) and motor recovery in adult mice. We showed that thoracic SCI resulted in an atrophy of GABAergic interneurons in the axotomized hindlimb cortex, as well as in a more widespread downregulation of parvalbumin expression. In parallel, spontaneous changes in the integrity of CSPG glycosaminoglycan (GAG) chains associated with PNNs occurred at the boundary between motor forelimb and sensorimotor hindlimb cortex, a region previously showed to undergo reorganization after thoracic SCI. Surprisingly, full digestion of CSPG GAG chains by intracortical chondroitinase ABC injection resulted in an aggravation of motor deficits and reduced sprouting of the axotomized CST above the lesion. Altogether, our data show that changes in the expression pattern of GABAergic markers and PNNs occur in regions of the sensorimotor cortex undergoing spontaneous reorganization after SCI, but suggest that these changes have to be tightly controlled to be of functional benefit.
Brain Research Institute, University of Zurich/ETH, Winterthurerstrasse 190, 8057, Zurich, Switzerland, orlando@hifo.uzh.ch.
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D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D059330:GABAergic Neurons / Q000378:metabolism; D006614:Hindlimb / Q000294:innervation*; D007395:Interneurons / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity; D009044:Motor Cortex / Q000378:metabolism / Q000503:physiopathology*; D009415:Nerve Net / Q000378:metabolism / Q000503:physiopathology*; D009473:Neuronal Plasticity; D011712:Pyramidal Tracts / Q000378:metabolism / Q000503:physiopathology*; D020127:Recovery of Function; D066191:Sensorimotor Cortex / Q000378:metabolism / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D015415:Biomarkers; D011508:Chondroitin Sulfate Proteoglycans; D005680:gamma-Aminobutyric Acid