A mutant strain of Han-Wistar rat carries an autosomal recessive gene producing spastic paresis. Homozygous animals progressively develop tremor, ataxia and hind limb rigidity beginning 3-4 weeks postnatally. Death ensues at about 10 weeks when animals lose motor control and can no longer feed. Because of the similarities of some of these behavioral symptoms with those induced by cerebellar and brainstem dysfunction, the morphology and physiology of the cerebellum in mutant rats were investigated. Cerebellar Purkinje cells degenerate and asymmetrical disarrangement of the granule cell layer occurs in mutants. The cytoskeleton of Purkinje cells was examined in the mutants by immunohistochemically staining for neurofilament proteins. Alterations in the distribution and arrangement of neurofilament proteins in Purkinje cell perikarya and dendrites and abnormal swellings in axons were found. Functionally, a combined molecular and neurophysiological approach was used in which Xenopus laevis oocytes were injected with mRNA from mutant brains and the ability of the oocytes to express excitatory amino acid receptors was assessed. Oocytes injected with cerebellar mRNA from mutants displayed increased responses to glutamate and kainate. The increased response to excitatory amino acids agonists could represent upregulation of receptors which may be capable of inducing the degeneration of the Purkinje cells. These results suggest that this mutant might be a developmental model of glutamate/kainate neurotoxicity.
|Original language||English (US)|
|Number of pages||15|
|State||Published - Dec 1 1992|
ASJC Scopus subject areas
- Clinical Neurology