Elevated monoamine levels in the cerebral hemispheres of microencephalic rats treated prenatally with methylazoxymethanol or cytosine arabinoside.

Abstract

Abstract: Methylazoxymethanol (MAM) injection to rats on day 15 of gestation caused a significant rise in monoamine concentrations (1.6, 2.0, and 2.8 times the control value for serotonin, norepinephrine, and dopamine, respectively) 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‐induced microencephaly. The decrease of DNA content and the 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, suggesting an important role played by this enzyme in the elevation of serotonin content. Although the marked decrease of DNA content in the cerebral hemispheres of MAM‐treated rats indicates a loss of cerebral cells due to prenatal MAM poisoning, the kind of cells destroyed remain to be studied. That the remaining neurons, axons, and oligodendroglia were intact was suggested by the normal activity of CNPase.