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Published on: December 15, 2014
Integrity of cortical perineuronal nets influences corticospinal tract plasticity after spinal cord injury
1Brain Research Institute, University of Zurich/ETH, Winterthurerstrasse 190, 8057, Zurich, Switzerland, orlando@hifo.uzh.ch.
Insights
Spinal cord injury alters brain networks, affecting motor neurons and chondroitin sulphate proteoglycans (CSPGs) in perineuronal nets (PNNs). These PNN changes are crucial for motor recovery after injury.
Area of Science:
- Neuroscience
- Extracellular Matrix Biology
- Spinal Cord Injury Research
Background:
- Injury-induced neuronal plasticity declines postnatally, coinciding with increased chondroitin sulphate proteoglycans (CSPGs) forming perineuronal nets (PNNs) around specific neurons.
- PNNs ensheath parvalbumin-expressing GABAergic interneurons, influencing neuronal function and plasticity.
Purpose of the Study:
- To investigate the relationship between PNN CSPG integrity, corticospinal tract (CST) remodeling, and motor recovery following spinal cord injury (SCI) in adult mice.
- To understand the role of PNNs in the sensorimotor cortex after thoracic SCI.
Main Methods:
- Utilized a mouse model of thoracic spinal cord injury (SCI).
- Analyzed changes in GABAergic interneurons and parvalbumin expression in the sensorimotor cortex.
- Assessed PNN CSPG glycosaminoglycan (GAG) chain integrity.
- Administered intracortical chondroitinase ABC to digest CSPG GAG chains.
Main Results:
- Thoracic SCI led to GABAergic interneuron atrophy and reduced parvalbumin expression in the hindlimb cortex.
- Spontaneous alterations in PNN CSPG GAG chain integrity were observed at the sensorimotor cortex border.
- Chondroitinase ABC treatment worsened motor deficits and decreased CST sprouting above the lesion.
Conclusions:
- SCI induces changes in GABAergic markers and PNNs within reorganizing sensorimotor cortex regions.
- These PNN modifications following SCI require precise regulation for beneficial functional outcomes.
- PNN integrity plays a complex role in motor recovery and CST plasticity after SCI.
Abstract:
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.
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