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.