大鼠脑发育期甲状腺激素对突触体素表达的影响

目的 探讨甲状腺激素对发育关键期大鼠大脑皮层、海马各区域突触体素表达的作用及影响.方法 Wistar大鼠分为4组:(1)甲减组:孕鼠自第5天起给予0.02%甲疏咪唑饮水,出生仔鼠即为先天甲减鼠;(2)T4替代组:孕鼠司样自第5天起给予0.02%甲巯咪唑饮水,仔鼠于出生当日起腹腔注T4,剂量为每日 0.02μg/g;(3)T4甲亢组:正常仔鼠于出生当日起腹腔注射T4,剂量为每日0.4μg/g;(4)正常对照组:孕鼠采用标准饲料和饮用自来水,其仔鼠作为正常对照组.采用原位杂交法对突触体素mRNA阳性信号表达进行定性及定量的测定.结果 (1)正常对照组在大脑顶叶皮层、海马突触体素表达模式基本相同且具有层状分布的特点.出生当日表达很低,在第4天表达最高.以后,随日龄增加而逐渐减少,至第30天表达水平基本接近于成年鼠水平.(2)甲减组大脑顶叶皮层和海马各时点突触体素表达均明显低于正常对照组(P＜0.01);甲减组表达高峰延迟3天,在第7天达到高峰.(3)T4-替代组在出生后第4、7、14、21、30天突触体素表达较同日龄甲减组明显增加,但仍低于同日龄正常对照组(P＜0.05或P＜0.01,除第7天海马DG区P＞0.05).(4)T4-甲亢组突触体素表达在第14、21、30天较同日龄正常对照组明显增加(P＜0.05或P＜0.01).结论在脑发育关键期,甲状腺激素的减少及T4-替代和T4-甲亢改变了大鼠大脑皮层、海马各区域突触体素的表达和时相性,进一步影响了该区域突触的发生及相关神经回路的建立,出现神经元的旷置或错误神经通路,阻碍了脑发育与功能成熟.而及时T4-替代治疗是纠正由于甲状腺激素缺乏而造成的中枢神经系统突触发育障碍的重要方法.

Effects of thyroid hormone on the synaptophysin expression of the developing rat brain

Objective To study the effects of thyroid hormone (TH) on synaptophysin (syn) expression in rat cortex and hippocampus during developing period. Methods The experimental animals were divided into four groups: (1) Hypothyroidism group: the pregnant maternal rats had been given 0.02% methimazole(MM)water since 5 days, the infant rats suffered from innate hypothyroidism. (2)T4 substitution group: innate 0 days. (4)Normal control group: The pregnant rats were given a normol diet and water, yielding infant rats used as normal matched control. The expression of synaptophysin mRNA were measured by in site hybridization. Results (1) In the normal control group synaptophysin expression showed a characteristics layer distribution in the cortex and hippocampus. The expression was very low at O day, the peak of expression was at 4 days. During the following days, the expression was reduced gradually, reaching nearly the level in the adulthood by 30 days. (2)Synaptophysin expressions in hypothyroidism group were significantly lower than those in normal control group(P＜0. 01). In hypothyroidism group the peak of synaptophysin expression was delayed by 3 days, attaining the high peak on 7 days. (3) Synaptophysin expressions in T4 substitution group were significantly higher than those in hypothyroidism group at 4 days, 7 days, 14 days, 21 days, and 30 days, but were still lower than the levels in normal group(P＜0.05 or P＜0.01, except 7 days synaptophysin expression at hippocampus DG,P＞0.05). (4)Synaptophysin expressions in T4 hyperthyroidism group were significantly higher than those in normal control group at 14 days、21 days、30 days(P＜0.05 or P＜0. 01). Conclusion The results suggested that reduced thyroid hormone, T4 substitution, and T4 hyperthyroidism led to the changes of synaptophysin expression in the rat cortex and hippocampus, resulting in an adverse effect on synapses occurrence and related nerve circuit establishment,with appearance of peerless neuronal place or mistaken nerve thoroughfare, thus hindering the development and function of the brain. Timely T4 substitution therapy is an important way to correct the disturbance in synapses development of the central nervous system due to deficient thyroid hormone.