DEVELOPMENT OF CHOLINERGIC NEURONS IN RAT-BRAIN REGIONS - DOSE-DEPENDENT EFFECTS OF PROPYLTHIOURACIL-INDUCED HYPOTHYROIDISM

The effects of hypothyroidism on development of cholinergic system in brain regions (prefrontal cortex and hippocampus) were evaluated by me asuring choline acetyltransferase (ChAT) activity and hemicholinium-3 binding to the high-affinity choline transporter. Various degrees of t hyroid deficiency were produced by perinatal exposure to propylthioura cil (PTU) in drinking water ranging from 5 ppm (mg/l) to 25 ppm beginn ing at gestational day 18 until postnatal day 21. ChAT. a marker for c holinergic nerve terminals, was reduced by PTU in a dose-dependent man ner. Concomitant with the enzyme deficits, hemicholinium-3 binding was elevated, suggesting an increase in neuronal impulse activity. Althou gh similar changes were seen in both brain regions examined, the magni tude and duration of these changes were more definitive in the prefron tal cortex. Nonetheless, these neurochemical alterations appeared to b e recoverable when the rats returned to a euthyroid state, and no furt her changes were observed as the animals reached adulthood. In compari son, data reported in a succeeding article indicate that deficits in c ognitive function were first seen in weanling hypothyroid rats, but th at the behavioral impairments lasted well into adulthood when thyroid status and cholinergic parameters in the brain appeared to have recove red to normal. These results suggest that alterations of cholinergic s ystem caused by perinatal hypothyroidism are associated with neurobeha vioral deficits at weaning, and these developmental deviations may cau se permanent impairment of cognitive function despite recovery from th e hormonal imbalance at adult ages. Published by Elsevier Science Inc.