A neurochemical study of experimental microencephalic rat.

Methylazoxymethanol (MAM) injection to pregnant rats on day 15 of gestation caused a significant rise in monoamine concentrations accompanying a decrease in the brain weight and DNA content in the cerebral hemispheres of the offspring at 3 months of age; in the brain stem, these changes were much smaller. Similar change of monoamine concentrations was observed in cytosine arabinoside (ara-C)-induced microencephaly. The decrease of DNA content and elevation of monoamine levels were lower with MAM-injection on day 15, 13 or 17 of gestation (in that order). Serotonin content of the MAM-treated cerebral hemispheres was already 50% higher than the control immediately after birth. The activity of tryptophan hydroxylase in the MAM-treated cerebrum was 1.6 times the control value, with no change in the brain stem, while the concentration of tryptophan in the brain and plasma was equal to the control value. That the remaining neurons, axons, and oligodendroglia were intact was suggested by the normal activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) [EC 3.1.4.37] and levels of brain specific proteins. When neonatal rats were injected with ara-C, a decrease of DNA content per cerebellum and an elevation of monoamine concentrations in the cerebellum were found. The neonatal administration of ara-C caused an elevation of CNPase activity and myelin protein content in the cerebellum, suggesting a relative increase in myelin concentration as a result of hypoplasia of granule cells.