Changes in Selected Brain Neurotransmitters and Their Metabolites in the Lamb after Thyroidectomy during the Last Two Trimesters of Gestation or the Early Neonatal Period

Abstract

To evaluate in a development context the effect of congenital hypothyroidism on concentrations of the neurotransmitters norepinephrine, dopamine, and serotonin (5HT) in selected brain areas of the ovine fetus, we studied the effect of thyroidectomy at three ages on the concentrations of these neurotransmitters and their major metabolites, homovanillic acid and 5-hydroxyindoleacetic acid. Fetuses underwent thyroidectomy at 90-95 or 105-115 d gestation (term = 147-150 d) or 1-5 d after birth. Approximately 25 d after thyroidectomy, at d 120-125 or 130-135 of gestation or 25-30 d after birth, respectively, the ewes were killed and fetal brains removed. Neurotransmitters and their metabolites were measured by HPLC with electrochemical detection. Thyroidectomy in the 2nd trimester increased 5HT in five brain areas: anterior hypothalamus, dorsal medial hypothalamus, pons, medulla, and cerebellum. Thyroidectomy in the 3rd trimester increased 5HT in the pons and medulla, increased norepinephrine in the dorsal medial hypothalamus and pons, and increased homovanillic acid in the posterior hypothalamus. Thyroidectomy in the newborn period decreased NE in the anterior hypothalamus, ventral medial hypothalamus, and midbrain, decreased 5-hydroxyindoleactic acid in the posterior hypothalamus, lateral hypothalamus, dorsal medial hypothalamus, and ventral medial hypothalamus, and decreased homovanillic acid in the dorsal medial hypothalamus and ventral medial hypothalamus. From these data we conclude the following: 1) Hypothyroidism causes changes in neurotransmitter concentrations only in selected brain areas of the ovine fetus, rather than causing generalized and similar changes in all brain areas; and 2) 5HT 5-hydroxyindoleacetic acid concentrations are affected more often than the other neurotransmitters evaluated, perhaps because the 5HT neurotransmitter system is developing at these times.