Retinoid receptors in chronic degeneration of the spinal cord: observations in a rat model of amyotrophic lateral sclerosis
2007
Jokic, Natasa | Ling, Yong Yong | Ward, Rachael E. | Michael-Titus, Adina T. | Priestley, John V. | Malaspina, Andrea
Changes in distribution and expression of retinoid receptors may be part of a spinal cord protective response to acute injury and to chronic degeneration. In this study, we have combined RNA and protein expression analysis to characterize the expression profile of retinoid receptors in the lumbar spinal cord of the superoxide dismutase 1 G93A mutant rat model of amyotrophic lateral sclerosis, a fatal neurodegenerative disorder causing extensive motor neuron loss. We also report a nonsignificant change in RNA expression of binding proteins and metabolizing enzymes for retinol and retinoic acid in the mutant rat spinal cord at end-stage disease. Only retinoid X receptor beta (RXRbeta), and to a lesser extent retinoic acid receptor beta and alpha (RARbeta/alpha) were reliably detected in lumbar spinal cord at an early pre-symptomatic phase and throughout the disease progression. The expression of RXRbeta in lamina II neurons in the dorsal horn of transgenic and wild type (WT) animals was associated with extensive astrocyte staining in end-stage lumbar spinal cord from transgenic rats. RARbeta and RARalpha diffuse staining of large motor neurons in the pre-symptomatic transgenic and in the WT lumbar cord appear to decline in end-stage disease, when a selective and strong gamma motor neuron RARalpha staining becomes evident. As gliosis and motor neuron loss are key pathogenic features in amyotrophic lateral sclerosis, the selective expression of retinoid receptors in astrocytes and motor neurons may provide further clues to the role of retinoid signalling in neurodegeneration and suggest new treatment strategies based on retinoid-modulating agents.
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