On the Mechanism of Irreversible Brain Damage Caused by Perinatal Thyroid Hormone Deficiency
Thyroid hormone-processing neural systems appear and become organized during the critical phase of thyroxine-dependent brain development (1). Hypothyroidism during that period causes irreversible mental impairment. Because lack of aromatic amino acids permanently damages developing neural systems which require them for neurotransmitter synthesis, we proposed permanent damage to thyroid hormone-processing systems may account for the cerebral manifestations of adult cretinism. To test this hypothesis, we studied the fate of i.v. 125I-labeled T3 and T4 in hippocampus and cerebellum, known targets of perinatal thyroid hormone deficiency, in serial film autoradiograms (ARGs), prepared from 50 day old rats made hypothyroid from −5 to +16 days of life by PTU (neoPTU). For comparison, film ARGs were prepared after i.v. 2-deoxyglucose given to neoPTU and control (C) rats. Results: The highly resolved labeling patterns seen in selected layers of hippocampus and cerebellum of C rats given labeled thyroid hormones were blurred and distorted in neoPTU. When viewed at the same level of resolution, differences seen could not be accounted for by changes in glucose metabolism of tissue morphology. Conclusion: The prediction that thyroid hormone deficiency during the critical phase would lead to permanent abnormalities in thyroid hormone processing in adult brain was borne out by the evidence gained in these studies.
KeywordsThyroid Hormone Aromatic Amino Acid Critical Phase Require Amino Acid Irreversible Brain Damage
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