Neurochemical characterization of embryonic brain development in trisomy 19 (Ts19) mice: Implications of selective deficits observed for abnormal neural development in aneuploidy

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Abstract
In this study, we examined the neurochemical profiles of selected brain regions (cerebral hemispheres, diencephalon/brainstem) in fetal (day 14 to 18 gestation) trisomy 19 (Ts19) mice. The neurochemical characteristics we observed in Ts19 mice were quite different from those we observed previously in Ts16 mice. Choline acetyltransferase (ChAT) activity was reduced significantly in the cerebral hemispheres, but not in the brainstem/diencephalon, of the fetal Ts19 mouse brain, suggesting a selective vulnerability of telencephalic cholinergic neurons. Additionally, the activity of glutamic acid decarboxylase (GAD) was reduced significantly in both hemispheres and diencephalon/brainstem of late gestation Ts19 fetuses, suggesting a selective vulnerability of GABAergic neurons as well. While the levels of catecholaminergic and dopaminergic markers were reduced significantly at late gestational ages, the relative rate of turnover of dopamine (DA), measured by the ratio of DOPAC/DA, was elevated significantly in Ts19 mice. Neither reduction in the thickness of various cellular zones of the cerebral cortex nor reduced cell density of the cerebral cortex accounts for the alterations in neurochemical parameters observed in Ts19 mice. These results suggest that the effects of the triplication of specific genes on the respective chromosomes, rather than a generalized disruption of developmental homeostasis resulting from extra chromosomal material, may produce selective alterations in neurochemical and neuroanatomical markers observed in these two mouse trisomies.