[A neurochemical study of rat brain maldevelopment induced by MAM treatment at different stages of gestation].
The regional levels of several cell marker proteins in the brain and the ability of operant discrimination learning on a multiple fixed ratio (FR), fixed interval (FI) schedule were determined in rats with microencephaly induced by prenatal treatment with methylazoxymethanol (MAM), an antimitotic agent, on the 11 th to 13 th days (Group A) or on the 15 th day (Group B) of gestation. The cell marker proteins were determined with a sensitive enzyme immunoassay. Neuron-specific enolase (NSE; gamma gamma-enolase) had a significantly lowered level in the neocortex anterior in Group A. Non-neuronal enolase (NNE; alpha alpha-enolase) was significantly reduced in the superior colliculus, lateral geniculate body and optic nerve, but increased 1.5 fold in the retina in Group A. S-100b protein, a marker of astroglial cells, showed no significant change. As for the learning performance, the Group B animals showed an elevated behavioral activity and made evident discrimination between the FI and FR schedule. But Group A animals had prolonged FR components requiring responses to light on, and their spontaneous activity counts recorded by Automex showed an inhibition of behavior in light environments. These findings suggest a causative role of some developmental abnormality in the central visual system, indicated by the aberrant cell marker levels, in the disturbed learning ability of the Group A animals.
Nagayoshi
M
M
Hirata
Y
Y
Tamaru
M
M
Sugimoto
S
S
Shimizu
J
J
Hirabayashi
K
K
Matsutani
T
T
D000014:Abnormalities, Drug-Induced; D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D001391:Azo Compounds / Q000633:toxicity*; D001921:Brain / Q000196:embryology* / Q000473:pathology; D001923:Brain Chemistry; D003216:Conditioning, Operant / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects; D005260:Female; D005865:Gestational Age; D008124:Locomotion / Q000187:drug effects; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives / Q000633:toxicity*; D008831:Microcephaly / Q000139:chemically induced* / Q000523:psychology; D009929:Organ Size / Q000187:drug effects; D010751:Phosphopyruvate Hydratase / Q000032:analysis; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D009418:S100 Proteins / Q000032:analysis
D000477:Alkylating Agents; D001391:Azo Compounds; D009418:S100 Proteins; D008746:Methylazoxymethanol Acetate; D010751:Phosphopyruvate Hydratase; C030667:methylazoxymethanol