Premium
Conditional Sox9 ablation reduces chondroitin sulfate proteoglycan levels and improves motor function following spinal cord injury
Author(s) -
McKillop William M.,
Dragan Magdalena,
Schedl Andreas,
Brown Arthur
Publication year - 2013
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22424
Subject(s) - chondroitin sulfate proteoglycan , spinal cord injury , spinal cord , astrocyte , aggrecan , perineuronal net , glial scar , sox9 , anatomy , medicine , neuroscience , chondroitin sulfate , biology , pathology , central nervous system , gene expression , glycosaminoglycan , biochemistry , alternative medicine , osteoarthritis , articular cartilage , gene
Chondroitin sulfate proteoglycans (CSPGs) found in perineuronal nets and in the glial scar after spinal cord injury have been shown to inhibit axonal growth and plasticity. Since we have previously identified SOX9 as a transcription factor that upregulates the expression of a battery of genes associated with glial scar formation in primary astrocyte cultures, we predicted that conditional Sox9 ablation would result in reduced CSPG expression after spinal cord injury and that this would lead to increased neuroplasticity and improved locomotor recovery. Control and Sox9 conditional knock‐out mice were subject to a 70 kdyne contusion spinal cord injury at thoracic level 9. One week after injury, Sox9 conditional knock‐out mice expressed reduced levels of CSPG biosynthetic enzymes ( Xt‐1 and C4st ), CSPG core proteins (brevican, neurocan, and aggrecan), collagens 2a1 and 4a1, and Gfap , a marker of astrocyte activation, in the injured spinal cord compared with controls. These changes in gene expression were accompanied by improved hind limb function and locomotor recovery as evaluated by the Basso Mouse Scale (BMS) and rodent activity boxes. Histological assessments confirmed reduced CSPG deposition and collagenous scarring at the lesion of Sox9 conditional knock‐out mice, and demonstrated increased neurofilament‐positive fibers in the lesion penumbra and increased serotonin immunoreactivity caudal to the site of injury. These results suggest that SOX9 inhibition is a potential strategy for the treatment of SCI. © 2012 Wiley Periodicals, Inc.