Levothyroxine Rescues The Lead-induced Hypothyroidism And Impairment Of Long-Term Potentiation In Hippocampal CA1 Region Of The Developmental Rats

A marked reduction in myelination in neonatal hypothyroidism and a notable demyelination in Pb-poisoned infants demonstrate that the endpoint of lead （Pb） neurotoxicity resembles that of subtle hypothyroidism in children. It was hypothesized that Pb may alter thyroid hormone homeostasis of the CNS.Hippocampus is the most important targets of Pb.It is thyoid hormone sensitive and dependent.Interestingly, hypothyroidism also attacks on hippocampus.Chronic Pb developmental exposure has been associated with reduced growth and impaired the induction, magnitude, and duration of long-term potentiation （LTP）.The thyroid hormone replacement therapy has been reported to increase the hypothyroidism-induced impaired LTP.The present study was designed to investigat whether L-T₄（levothyroxine） administration could reverse the thyroid disequilibrium and impairment of LTP in rat hippocampus caused by Pb or PTU （propylthiourycil） exposure.Meanwile,the association between thyroid hormone homeostasis and LTP in CA1 area of hippocampus were authenticated.we have compared LTP amplitude and thyroid hormone, thyroid stimulating hormone（TSH） levels in groups of developmental Pb-exposed, PTU-exposed and control rats with or without L-T₄ treatment （20, 50 and 100 ug/kg through intraperitoneal injection）.The capacity of L-T₄ to decrease blood and hippocampal Pb levels in Pb-exposed rats was also examined.The results showed that T₃ （triiodothyronine） and T₄ （tetraiodothyronine） levels decreased accompanied with LTP amplitude decrease in CA1 area of hippocampus in the Pb or PTU-exposed group.L-T₄ treatment resulted in increases in the T₃ and T₄ levels and increases in the amplitude of LTP.TSH levels were also normalized following L-T₄ treatment. In addition, hippocampal and blood Pb concentration were partially reduced after L-T₄ treatment in rats developmentally exposed to Pb or PTU for 2 weeks following birth.These findings confirm the hypothesis that Pb-induced neurotoxicity may alter thyroid hormone homeostasis.The intellectual impairment of Pb is a result of central hypothyroidism due to the hypothalamic-pituitary-thyroid-axis dysfunction.