论文部分内容阅读
目的探索甲状腺激素通过神经生长因子(NGF)及其受体TrKA对大鼠顶叶皮层、海马部位中枢胆碱能神经元发育的作用。方法将Wistar大鼠分为3组:①甲状腺功能减退(甲减)组:从母鼠妊娠5～6d起饲以含0.02%的他巴唑饮用水;②甲状腺功能亢进(甲亢)组:仔鼠出生即日起,按体质量腹腔注射T4(0.4μg/g);③对照组:饲以普通饲料及饮用水。于出生后第14、21、28天,免疫组化法检测大鼠顶叶皮层、海马中胆碱乙酰转移酶(ChAT)阳性细胞,原位杂交法测定NGF、TrkA mRNA的表达。结果①出生后第21、28天顶叶皮层、海马中,甲减组(159.42±5.26、162.37±4.67,98.60±7.67、101.50±4.39)ChAT阳性细胞数较对照组(174.80±5.10、171.40±3.87,213.40±16.93、274.60±6.69)明显减少(P<0.05或<0.01),甲亢组(312.50±3.75、296.30±6.13,324.60±15.72、319.10±8.85)ChAT阳性细胞数较对照组明显增加(P<0.01);②对照组顶叶皮层、海马中,ChAT阳性细胞数、NGF、TrkA mRNA表达高峰期分别为第28、21、28天,甲亢组未见高峰期改变,而甲减组除TrkA mRNA表达高峰期未改变,仍为第28天外,ChAT阳性细胞数、NGF mRNA表达高峰期分别变为第21、28天;③在顶叶皮层、海马中,第14、21、28天NGF、TrkA mRNA表达甲减组均低于对照组(P<0.05或<0.01);第14、21天甲亢组与对照组相比,NGF mRNA明显升高(P<0.05或<0.01),TrkA mRNA各时点两组间比较差异均无统计学意义(P>0.05)。结论胆碱能神经元在脑发育期内对甲状腺激素失衡十分敏感,NGF、TrkA mRNA在发育过程中的变化对中枢胆碱能神经元的存活、发育可能起一定的调节作用,甲状腺激素可能通过NGF及其受体TrkA调节海马及顶叶皮层中枢胆碱能神经元的发育。
Objective To explore the effect of thyroid hormone (NGF) and its receptor TrKA on the development of central cholinergic neurons in the parietal cortex and hippocampus in rats. Methods Wistar rats were divided into three groups: ① hypothyroidism (hypothyroidism) group: from maternal pregnancy 5-6d with 0.02% methbazol drinking water; ② hyperthyroidism (hyperthyroidism) group: Aberdeen Rats from the date of birth, according to the body weight of intraperitoneal injection of T4 (0.4μg / g); ③ control group: fed with normal feed and drinking water. The expression of NGF and TrkA mRNA in rat parietal cortex and choline acetyltransferase (ChAT) positive cells in hippocampus were detected by immunohistochemistry on the 14th, 21st and 28th day after birth. Results ①The number of ChAT positive cells in the parietal cortex, hippocampus and hypothyroidism groups at the first and second postnatal days were (159.42 ± 5.26,162.37 ± 4.67,98.60 ± 7.67,101.50 ± 4.39) (174.80 ± 5.10,171.40 ± 3.87,213.40 ± 16.93,274.60 ± 6.69) (P <0.05 or <0.01). The number of ChAT positive cells in hyperthyroidism group (312.50 ± 3.75,296.30 ± 6.13,324.60 ± 15.72,319.10 ± 8.85) was significantly higher than that in control group P <0.01). ② In the control group, the peak numbers of ChAT positive cells, NGF and TrkA mRNA in the parietal cortex and hippocampus were 28, 21 and 28 days respectively. No peak change was observed in hyperthyroidism group, The peak of TrkA mRNA expression remained unchanged at the 28th day, and the number of ChAT positive cells and the peak of NGF mRNA expression became the 21st and 28th day, respectively. ③ In the parietal cortex and hippocampus, NGF (P <0.05 or <0.01). On the 14th and 21st day, the expression of NGF mRNA in hyperthyroidism group was significantly higher than that in the control group (P <0.05 or <0.01), while TrkA mRNA There was no significant difference between the two groups at any time point (P> 0.05). Conclusions Cholinergic neurons are very sensitive to the imbalance of thyroid hormones during brain development. The changes of NGF and TrkA mRNA may play a regulatory role in the survival and development of central cholinergic neurons. Thyroid hormones may pass NGF and its receptor TrkA regulate the development of central cholinergic neurons in the hippocampus and parietal cortex.