[3H]muscimol and [3H]flunitrazepam binding sites in the developing cerebellum of mice treated with methylazoxymethanol at different postnatal ages.
Two models of perturbed cerebellar ontogenesis were obtained by a single administration of methylazoxymethanol (MAM), a potent antimitotic agent, to mouse pups either on the day of birth (MAM0 mice) or at postnatal day 5 (MAM5 mice). The alterations of the cerebellar GABAergic system were studied by measuring glutamic acid decarboxylase activity, [3H]muscimol binding sites, which are known to be concentrated in the GABAA receptors in the internal granular layer, and [3H]flunitrazepam binding sites, which are more abundant in the molecular layer. The primary target of the antimitotic agent are the precursors of the glutamatergic and GABAceptive granule cells. In both models GABAergic structures, as revealed by GAD activity measurements, appear to be relatively spared, and recovery of granule cell numbers occurs during development in MAM5 mice. In MAM treated mice the number of [3H]muscimol binding sites (on a per cerebellum basis) decrease as the number of granule cells decrease, although some recovery occurred in MAM5 mice, but not in MAM0 mice. In MAM5 mice, [3H]flunitrazepam binding sites (on a per cerebellum basis) were relatively unaffected, while they were decreased significantly, but to a lesser extent than [3H]muscimol binding sites, in MAM0 animals. The more significant reduction of granule cell numbers and the cytoarchitectural disruption resultant from the more precocious application of the antimitotic appear responsible for the significant alteration and lack of recovery in MAM0 mice.
Bacon
E
E
Centre de Neurochimie du CNRS, Strasbourg, France.
Girard
C
C
de Barry
J
J
Gombos
G
G
D000818:Animals; D001665:Binding Sites; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D005445:Flunitrazepam / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000032:analysis / Q000378:metabolism; D008746:Methylazoxymethanol Acetate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D009118:Muscimol / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000187:drug effects; D013569:Synapses / Q000378:metabolism* / Q000502:physiology
D011963:Receptors, GABA-A; D009118:Muscimol; D008746:Methylazoxymethanol Acetate; D005445:Flunitrazepam; D005968:Glutamate Decarboxylase; C030667:methylazoxymethanol