Autoradiography of glutamate receptor binding in adult Lurcher mutant mice.
The mutation Lurcher, resulting from a gain of malfunction of the delta2 glutamate receptor expressed specifically by cerebellar Purkinje cells, causes a primary total loss of these neurons of the cerebellar cortex, as well as the secondary degeneration of cerebellar granule and inferior olive neurons. The distributions of glutamate receptors sensitive to amino-methylisoxazole-propionic acid (AMPA), to kainic acid (KA), and to N-methyl-D-aspartic acid (NMDA) as well as metabotropic sites (MET1 and MET2) were examined in wild type and Lurcher mice by quantitative autoradiography. This study was undertaken to determine the gene effect on the distribution of the various glutamate receptor subtypes, as well as how the cerebellar lesion affects the glutamatergic system in other brain regions. In cerebellum, there were postsynaptic AMPA and metabotropic receptors on Purkinje cells, postsynaptic NMDA receptors on granule cells, as well as KA receptors on granule cells or on parallel fibers. Taking into account surface areas, binding to all receptor subtypes was lower in the cerebellar cortex of Lurcher mutants than in wild type mice, while in the deep cerebellar nuclei only KA receptors were diminished. In other brain regions, the alterations followed always the same pattern characterized by a decrease of NMDA and KA receptors but with an increase of AMPA sites; these reciprocal changes were seen in thalamus. neostriatum, limbic regions, and motor cerebral cortical regions. Comparisons of glutamate receptor distribution in Lurcher mutants and in human autosomal cerebellar ataxia may permit further understanding of the role of glutamate-induced toxicity on neuronal death in these heredo-degenerative diseases.
Strazielle
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Centre de Recherche en Sciences Neurologiques, Faculté de Médecine, Université de Montréal, Qc, Canada.
Lalonde
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D000818:Animals; D001345:Autoradiography; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008818:Mice, Neurologic Mutants / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism*; D012016:Reference Values; D014018:Tissue Distribution
D017470:Receptors, Glutamate