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1.
Article in Chinese | WPRIM | ID: wpr-344335

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the behavioral development in adolescent rats of perinatal hypothyroidism and its relation to androgen receptor (AR) gene expression in the hippocampus.</p><p><b>METHODS</b>Perinatal hypothyroidism was induced by gavages 50 mg/d of propylthiouracil solution in 48 dams starting at embryonic day 15 through the lactation period. Twenty-four pups (M:F=1) of perinatal hypothyroidism were injected intraperitoneally with 2 microg T(4)/100 g BW daily from the day of birth to the age of 21 days (treatment group); 24 pups (M:F=1) without treatment were designated as hypothyroidism group. And 24 normal pups (M:F=1) served as the control group. The effects of perinatal hypothyroidism on the abilities to learn and retain memory traces and on behavior were observed in rats of both sexes at 60 days. Experiments were performed using models of conditioned "open" field test and passive avoidance reflexes. Hippocampus samples were collected and AR mRNA was detected by competitive RT-PCR.</p><p><b>RESULT</b>Perinatal hypothyroidism caused an increase of crossing number and decrease of rearing and defecation in both sexes. In treatment groups, only the crossing number in male didn't reach the normal level (P >0.05). In passive avoidance test, hypothyroidism groups showed more mistakes in both sexes and shorter latencies in males, the females performed better than males (P <0.01). The treatment groups performed significantly better than the age-matched hypothyroidism groups and reached the normal level (P >0.05). AR mRNA levels in hippocampus of hypothyroid group were lower than those of the controls in males, and the levels in treatment groups were significantly higher in comparison with the hypothyroidism groups (P <0.01). There were no significant differences among the three female groups (P >0.05). In male group, there was negative correlation between the number of crossing and AR mRNA in the hippocampus (r=-0.537, P=0.001), negative correlation between the number of mistake and AR mRNA (r=-0.532, P=0.001), and positive correlation between the latency and AR mRNA (r=0.564, P=0.000).</p><p><b>CONCLUSION</b>Perinatal hypothyroidism results in hyperactivity and anti-anxiety effects on adolescent rats, the sex difference is depleted, and also causes learning and memory impairment but the degree of influence higher in male than female. The decreased level of AR mRNA expression in hippocampus contributes to the change of behavioral ability in adolescent male.</p>


Subject(s)
Animals , Animals, Newborn , Behavior, Animal , Female , Hippocampus , Metabolism , Hypothyroidism , Metabolism , Male , Pregnancy , RNA, Messenger , Metabolism , Random Allocation , Rats , Rats, Sprague-Dawley , Receptors, Androgen , Metabolism , Sex Factors
2.
Chinese Journal of Pediatrics ; (12): 48-52, 2005.
Article in Chinese | WPRIM | ID: wpr-238067

ABSTRACT

<p><b>OBJECTIVE</b>During the critical period of brain development, insufficiency of thyroid hormone results in severe mental retardation and learning deficit. This study was designed to investigate the effects of hypothyroidism on apoptosis and the expression of Bcl-2 and Bax gene in the developing rat hippocampus neurons and to explore the mechanism of brain development regulated by thyroid hormone.</p><p><b>METHOD</b>Hypothyroidism was induced by administration of propylthiouracil (PTU, 50 mg/d) solution to the dams from gestational day 15 by gavage. Pups from both hypothyroid and control groups were harvested at postnatal day 1 (P1), P5, P10 and P15, respectively. Blood samples were collected at the time of death for the determination of thyroid hormone. Serum free tri-iodothyronine (FT(3)) and free thyroxine (FT(4)) were measured by using chemoluminescence. Hippocampus collected from the control and hypothyroid pups were examined under light and transmissional electron microscopy. Measurement of DNA fragmentation was carried out by agarose gel electrophoresis. The expression of Bcl-2 and Bax protein in the developing rat hippocampus neurons was performed by Western blotting.</p><p><b>RESULTS</b>Significantly lower circulating FT(4) and FT(3) levels confirmed the hypothyroid status of the experimental pups. The shrunken and contracted degenerations increased in hippocampus neurons of hypothyroid pups under light microscopy. Enhanced apoptotic cells were found in hippocampus neurons of hypothyroid pups under transmission electron microscopy, especially at P10 and P15. Extensive DNA fragmentation was seen throughout development in hippocampus of hypothyroid pups, but not in the euthyroid controls except for basal level at P10. The expression of Bcl-2 in the hippocampus neurons of hypothyroid pups was significantly lower than that of euthyroid controls at all stages of development (P1: 1.95 +/- 0.27 vs. 2.59 +/- 0.19, P < 0.05, P5: 1.86 +/- 0.24 vs. 2.47 +/- 0.17, P < 0.05, P10: 1.29 +/- 0.22 vs. 1.86 +/- 0.28, P < 0.05 and P15: 1.21 +/- 0.27 vs. 2.18 +/- 0.17, P < 0.01, respectively). The relative amount of expression varied significantly with age in the control pups. The level of Bcl-2 was high in hippocampus neurons of euthyroid at P1, P5, and decreased significantly at P10, and showed a trend of recovery at P15. Similar age-related variation in the expression of Bcl-2 gene was observed in the hypothyroid group at P1, P5 and P10, but the level was maintained low at P15. The expression of Bax in the hippocampus neurons of hypothyroid pups was significantly higher than that of control pups at all stages of development (P1: 1.69 +/- 0.14 vs. 1.24 +/- 0.23, P < 0.05, P5: 1.78 +/- 0.16 vs. 1.29 +/- 0.17, P < 0.05, P10: 1.92 +/- 0.18 vs. 1.45 +/- 0.14, P < 0.05 and P15: 1.86 +/- 0.14 vs. 1.51 +/- 0.12, P < 0.05, respectively). The ratio of Bcl-2/Bax in hippocampus neurons of hypothyroid pups was lower than that of age-matched controls (P1: 1.16 +/- 0.17 vs. 2.12 +/- 0.35, P < 0.05, P5: 1.05 +/- 0.16 vs. 1.94 +/- 0.36, P < 0.05, P10: 0.68 +/- 0.17 vs. 1.29 +/- 0.16, P < 0.05 and P15: 0.67 +/- 0.19 vs. 1.45 +/- 0.22, P < 0.01, respectively).</p><p><b>CONCLUSION</b>Thyroid hormone significantly prevents apoptosis of hippocampus neurons. Congenital hypothyroidism increases not only the extent but also the duration of apoptosis by down-regulation of the anti-apoptotic gene Bcl-2 and maintaining a high level of the pro-apoptotic gene Bax.</p>


Subject(s)
Animals , Animals, Newborn , Apoptosis , Physiology , Down-Regulation , Hippocampus , Metabolism , Hypothyroidism , Neurons , Metabolism , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Rats , bcl-2-Associated X Protein , Metabolism
3.
Article in Chinese | WPRIM | ID: wpr-355219

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of perinatal thyroid hormone deficiency on the expression of androgen receptor (AR) mRNA in cerebral cortex and hippocampus of rats.</p><p><b>METHODS</b>Perinatal hypothyroidism was induced by the administration of propylthiouracil (PTU) solution to the dams by gavage (50 mg/d) beginning at embryonic d15 throughout the lactational period. In the T(4) injected group hypothyroid rats were injected intraperitoneally with levothroxine (L-T(4)) 2 microg/100 g BW daily, starting from the day of birth. Cerebral cortex and hippocampus specimen were collected from controls,hypothyroid and T(4)-injected hypothyroid rats on postnatal d1, 5, 10, 15 and 20. Quantification of ARmRNA in cerebral cortex and hippocampus was performed with competitive RT-PCR using internal and external standardization.</p><p><b>RESULT</b>Age-related increasing ARmRNA levels were observed in neonatal rats, and those in male animals were significantly higher. AR expression was higher in the hippocampus than in the cerebral cortex. ARmRNA levels in the hypothyroid pups were lower than those in age-matched controls. The mRNA levels in the T(4)-injected hypothyroid pups were significantly higher compared with the age-matched hypothyroid pups, but in hippocampus ARmRNA expression did not reach normal levels in male rats at d10 and d20, in female at d15 and d20.</p><p><b>CONCLUSION</b>The expression of ARmRNA decreases in brain of rats with perinatal hypothyroidism. Treatment with thyroid hormone can recover ARmRNA expression in cerebral cortex, but not in hippocampus.</p>


Subject(s)
Animals , Animals, Newborn , Cerebral Cortex , Metabolism , Female , Hippocampus , Metabolism , Hypothyroidism , Metabolism , Pregnancy , Pregnancy Complications , Metabolism , RNA, Messenger , Genetics , Random Allocation , Rats , Rats, Sprague-Dawley , Rats, Wistar , Receptors, Androgen , Genetics
4.
Article in Chinese | WPRIM | ID: wpr-355218

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the mechanism for the apoptosis of hippocampus neuron induced by hypothyroidism in perinatal rats.</p><p><b>METHODS</b>Hypothyroidism was induced by administration of propylthiouracil (PTU, 50 mg/d) solution to the dams from gestational day 15 by gavage. Pups from both hypothyroid and control groups were harvested at 1, 5, 10 and 15d, respectively. Blood samples were collected at the time of death for the determination of thyroid hormone. Serum free triiodothyronine (FT(3)) and free thyroxine (FT(4)) were measured by chemoluminescence. Hippocampus specimens were collected from the control and hypothyroid pups.Mitochondia was examined under transmission electron microscopy. Translocation of apoptogenic molecules (Bax, cytochrome C and AIF) and activation of caspase-3 were analyzed by Western Blotting.</p><p><b>RESULT</b>Significantly low circulating FT(3) and FT(4) levels confirmed the hypothyroid status of the experimental pups. Electron microscopy showed that altered morphology of mitochondria significantly increased under hypothyroid conditions. The expression of Bax in the cytosol of hypothyroid pups was higher than that of control pups at all stages of development (P<0.05),and significantly higher in mitochondria (P<0.001). The expression of cytochrome c in the cytosol of hypothyroid pups was significantly higher than that of control pups at all stages of development (1,10 and 15 d:P<0.05, 5d: P<0.001), and lower in mitochondria (P<0.05). The expression of AIF in the cytosol of hypothyroid pups was higher than that of control pups at all stages of development (P<0.001), and significantly lower in mitochondria (1, 5d: P<0.001, 10, 15 d: P<0.01). he expression of caspase-3 P20 in the cytosol of hypothyroid pups was significantly higher as compared with that of the age-matched controls (1, 15d: P<0.01, 5,1 0 d: P<0.001).</p><p><b>CONCLUSION</b>The intrinsic death pathway in mitochondria may be one of the mechanisms with which hypothyroid induces apoptosis of hippocampus neuron in developing rats.</p>


Subject(s)
Animals , Animals, Newborn , Apoptosis , Physiology , Female , Hippocampus , Pathology , Hypothyroidism , Pathology , Neurons , Pathology , Pregnancy , Pregnancy Complications , Pathology , Propylthiouracil , Rats , Rats, Wistar
5.
Article in Chinese | WPRIM | ID: wpr-675901

ABSTRACT

0.05). Conclusion Peaks of serum gonadotropin and sex hormone concentrations are reached at 2~4 months of age and sexual dimorphism is shown, suggesting that in boy and girl infants, different mechanisms may be involved in regulating the development of gonads.

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