Changes in AMPA receptor binding in an animal model of inborn paroxysmal dystonia.
Previous pharmacological studies suggested that glutamatergic overactivity contributes to manifestation of dystonic attacks in mutant hamsters (dt(sz)), a model of idiopathic paroxysmal dystonia in which episodes of dystonia occur in response to stress. In the present study, [(3)H]AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate) receptor binding was determined by autoradiographic analyses in 41 brain (sub)regions of dt(sz) hamsters under basal conditions, i.e., in the absence of dystonia, and in a group of mutant hamsters that exhibited severe stress-induced dystonic attacks immediately prior to sacrifice. In comparison to nondystonic control hamsters the basal [(3)H]AMPA binding was significantly higher in the ventromedial and ventrolateral caudate putamen, the anterior cingulate cortex, the hippocampus, and the lateral septum of dystonic brains. During dystonic attacks the [(3)H]AMPA binding was significantly lower in the dorsomedial, dorsolateral, and posterior caudate putamen; the ventromedial thalamus; and the frontal cortex of mutant hamsters compared with control animals that were exposed to the same external stimulation. The basal increase in AMPA receptor density within limbic structures may contribute to the susceptibility of stress-inducible dystonic episodes in mutant hamsters. Since AMPA receptor activation is known to cause a fast reduction of the affinity and an internalization of postsynaptic AMPA receptors, the latter finding could reflect a glutamatergic overactivity within the striato-thalamo-cortical circuit during the expression of dystonia, which is in line with previous neurochemical and pharmacological data in dt(sz) hamsters.
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000235:genetics; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006224:Cricetinae; D004195:Disease Models, Animal; D004421:Dystonia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D009154:Mutation; D018091:Receptors, AMPA / Q000378:metabolism*; D012016:Reference Values; D013312:Stress, Physiological / Q000503:physiopathology; D014018:Tissue Distribution; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000493:pharmacokinetics
D018091:Receptors, AMPA; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid