Effects Of Hypothyroidism On The Development Of Brain Functions In Rat

Objective:The abnormal changes of somatosensory, motor, emotional behavior and learning andmemory functions and cell apoptosis of the brain tissue had been observed in the rat withhypothyroidism in the different period of brain development to further probe into theactions of thyroid hormone on brain development and the related action mechanisms,which has an important guiding significance for the prevention and treatment of infantswith congenital hypothyroidism.Methods:The rat pups with hypothyroidism in different periods of brain development wereinduced by methimazole solution of0.3g·L-1mass concentration added in the drinkingwater. The rat pups were randomly divided into4groups, group E1（hypothyroidismduring embryo）, group P1（hypothyroidism from postnatal day1to50）, group P14（hypothyroidism from postnatal day14to50）,group P30（hypothyroidism from postnatalday30to50） and group N （control）. Serum free triiodothyronine （FT₃） and thyroxine ortetraiodothyronine （FT₄） of the rat were determined by radioimmunoassay. At postnatalday50, the cold and hot reaction time, over hanging and inclined plane test, open fieldtest, and Y maze test of the rat were measured to evaluate the functions of somaticsensation, body movement, emotion behavior and learning and memory respectively. Theapoptosis of the brain tissues at postnatal day50in rat was determined via terminaldeoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL） staining,and the positive staining cells were counted via an image analysis system.Results:1. The serum concentrations of FT3and FT4were significantly lower in the rat of theexperimental groups. 2. The cold and hot reaction times prolonged significantly in the rat in group P1and P14,and they were not significantly greater in the rat in group E1and P30than in groupN.3. The over hanging times shortened significantly in the rat in group P1and P14, andthey were not significantly smaller in the rat in group E1and P30than in group N.The turning times of inclined plane prolonged significantly in the rat in group P1, P14and P30, and they were not significantly greater in the rat in group E1than in groupN.4. The crossing scores of open field test increased significantly in the rat in group P1,P14and P30, and they were not significantly higher in the rat in group E1than ingroup N. The rearing numbers and defecation numbers in open field test decreasedsignificantly in the rat in group P1, P14and P30, and they were not significantlysmaller in the rat in group E1than in group N.5. The correct reaction rates in Y maze test decreased significantly in the rat in group P1,P14and P30, and the learning days increased and memory keeping rates decreasedsignificantly in Y maze test in the rat in group P1and P14. The abilities of learningand memory in the rat in group E1were not significantly different from that in groupN. The learning days and memory keeping rates in the rat in group P30were notsignificantly different from that in group N.6. The apoptosis cells in the cerebral cortex increased significantly in the rat in group P1,P14and P30. The apoptosis cells in the hippocampi increased significantly in the ratin group P1. The apoptosis cells in the cerebellum increased significantly in the rat ingroup P1and P14.Conclusions:1. The development of the functions of somatic sensation, body movement, emotionbehavior and learning and memory retards significantly in the rat withhypothyroidism in the different period of brain development. 2. The retarded brain development in the rat with hypothyroidism in the different periodof brain development is closely related to the increased apoptosis in the brain tissues.3. The critical action periods of thyroid hormone for the development of different brainfunctions are different in rat.