甲状腺激素对大鼠脑海马发育期神经元烟碱受体α4亚单位表达的影响

摘要

Objective To investigate the effects of thyroid hormone( TH )on the nicotinic acetylcholine receptor α4( nAchRα/4 )expression in the developing period of rat hippocampus. Methods The Wistar rats were divided into normal group ( n = 42 ) and hypothyroidism group ( n = 36 ). The hypothyroidism model of rats was established by pre-treatment with thiamazole. The brain tissues of rats were collected at the postnatal day 0,4,7 ,14 .21 .30 and 120 in 2 groups. The expression of nAchRα4 mRNA in hippocampus was detected by in situ hybridization method. Results ①The nAchRα4 mRNA expression was significantly different at different postnatal days and distributed by layer. The nAchRα4 mRNA expression was very low at postnatal day 0 ( POd ), peaked at postnatal day 14 or 21 ,and then decreased to the level of adulthood rat( at postnatal day 120 ).②The peak expression of nAchRα4 mRNA was 4 - 5 times of the adulthood level in CAI of normal rats. about 8 times in CA2 , CA3 sectors , and about 5 times in dentate gyrus. ③Expression of nAchRα4 mRNA in hypothyroidism group was significantly lower than that in normal group( P ＜0. 001 ). The peak of nAchRa4 mRNA expression occurred at the same time in hypothyroidism group and normal group. Conclusion The results suggest that in the critical period of hrain growth, thyroid hormone decrease c:ould lead to the change of nAChRα4 mRNA expression in the rat hippocampus, and further affect the occurrence of synapses and establishment of related nerve circuit, the peerless of the neuronal place or mistaking of nerve thoroughfare , which may obstruct the brain development and function maturation.%目的 探讨甲状腺激素(TH)对发育关键期大鼠脑海马区域神经元烟碱受体α4亚单位(nAChRα4)表达的作用和影响.方法 实验分成正常对照组(n=42)和甲减组(n=36).选用甲巯咪唑(MM)复制甲状腺机能减退大鼠模型,收集出生后第0,4,7,14,21,30,120天的正常、甲减仔鼠脑组织,每组6只.采用原位杂交组织化学法检测发育关键期仔鼠大脑海马区域神经元烟碱受体α4亚单位(nAChRα4)的表达变化情况.结果 ①正常对照组nAChRα4 mRNA在生后不同发育阶段的表达变化明显且具有层状分布的特点.生后第0天表达很低,在生后第14-21天nAChRα4 mRNA表达最高,然后下降,直至成年鼠水平(生后第120天).②正常对照组nAChRα4 mRNA海马CA1区阳性信号表达高峰(生后第21天)是成年鼠的4-5倍,海马CA2、CA3区阳性信号表达高峰(生后第21天)是成年鼠的8倍左右,海马齿状回(DG)区阳性信号表达高峰(生后第14天)是成年鼠的5倍左右.③甲减组nAChRα4 mRNA表达在各时点均明显低于正常对照组(P<0.001).甲减组表达的高峰时间与正常对照组的高峰时间相一致,无高峰延迟.结论 在脑发育关键期,甲状腺激素水平的减少改变了大鼠脑海马神经元烟碱受体α4亚单位的表达,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,这可能阻碍了脑发育与其功能的成熟.