Maternal hypothyroxinemia disrupts neurotransmitter metabolic enzymes in developing brain

Maternal thyroid status influences early brain development and, consequentl y, cognitive and motor function in humans and rats. The biochemical targets of maternal thyroid hormone (TH) action in fetal brain remain poorly defin ed. A partially thyroidectomized rat dam model was therefore used to invest igate the influence of maternal hypothyroxinemia on the specific activities of cholinergic and monoaminergic neurotransmitter metabolic enzymes in the developing brain. Maternal hypothyroxinemia was associated with reduced monoamine oxidase (MA O) activity in fetal whole brain at 16 and 19 days gestation (dg). A simila r trend was observed for choline acetyltransferase (ChAT) activity. In cont rast, DOPA decarboxylase (DDC) activity was markedly elevated at 21 dg. Fur ther study of these enzymes at 14 dg showed no differences between normal a nd experimental progeny - suggesting they become TH sensitive after this ag e. Tyrosine hydroxylase (TyrH) and acetylcholinesterase (AChE) activities w ere unaffected prenatally. During postnatal development, the activities of TyrH, MAO, DDC and, to a lesser extent, AChE were increased in a brain regi on- and age-specific manner in experimental progeny. The prenatal disturbances noted in this study may have wide-ranging consequ ences since they occur when neurotransmitters have putative neurotropic rol es in brain development. Furthermore, the chronic disturbances in enzyme ac tivity observed during postnatal life may affect neurotransmission, thereby contributing to the behavioural dysfunction seen in adult progeny of hypot hyroxinemic dams.