Disability-specific genes GRIN1, GRIN2 and CNR1 show injury-dependent protein expression in the lumbar spinal cord of CCI rats

Abstract

The sensory changes triggered by peripheral nerve injury result from functional changes in both neurons and glia in the dorsal horn of the spinal cord. Whether the disrupted affective-motivational states often comorbid with injury-evoked changes in sensation are driven directly by these functional changes is a question only recently investigated. Using a combination of GeneChip microarrays and RT-PCR techniques we identified differences in mRNA expression unique to rats with sustained changes to their social behaviour following sciatic nerve chronic constriction injury (CCI). Amongst these changes were the mRNAs encoding several of the NMDA subunits and the CB1 receptor. However, as protein translation is not a necessary consequence of the upregulation or downregulation of genes we decided to evaluate the functional significance of our initial observations using immunohistochemical detection of their translated protein products to determine their location and abundance in the lumbar spinal cord. Spinal cord tissue from rats with (‘Affected’), and without (‘Unaffected’) changes in social behaviour after CCI was compared with tissue from uninjured controls. The expression of NMDA-1 (NR1) subunit, NMDA-2D subunit, Cannabinoid Receptor 1 (CB1), Glucocorticoid Receptor (GR) and Glial Fibrillary Acidic Protein (GFAP) immunoreactivities was quantified for these rats and revealed that nerve injury increased the expression of NMDA-2D, CB1 and GFAP immunoreactivity compared to uninjured controls. However, these changes were not specific to rats whose social behaviours were ‘Affected’ or ‘Unaffected’ by the nerve injury. Our data thus suggest that the development and expression of changes in social behaviour seen in a proportion of rats following CCI are unlikely to be directly related to the spinal changes in NMDA-2D, CB1 and GFAP expression induced by the nerve injury.