Effects of CAMK4⁃EGR3 signaling axis on hippocampal neuronal dendrites in congenital hypothyroidism rats
Author:
Affiliation:
Fund Project:
摘要
|
图/表
|
访问统计
|
参考文献
|
相似文献
|
引证文献
|
资源附件
|
文章评论
摘要:
目的：探讨先天性甲状腺功能减退症（congenital hypothyroidism，CH）大鼠海马中Ca2+/钙调蛋白依赖性蛋白激酶Ⅳ（Ca2+/calmodulin-dependent protein kinase Ⅳ，CAMK4）及早期生长反应蛋白3（early growth response protein 3，EGR3）信号轴对神经元树突发育的影响。方法：1日龄、7日龄及21日龄SD大鼠制备CH模型，分为CH组与对照组。采用转录组测序、q-PCR、Western blot分别检测CAMK4与EGR3的表达情况，细胞免疫荧光观察神经元树突生长情况。结果：①对照组海马组织CAMK4及EGR3的蛋白表达呈时间依赖性上升，CH组的表达则显著低于对照组（P < 0.05）；②原代海马神经元中敲降CAMK4后，EGR3的表达相应降低，同时海马神经元树突平均长度较对照组减小；③CH原代海马神经元给予三碘甲腺原氨酸（3，5，3′-triiodothyronine，T3）刺激后，CAMK4的蛋白表达水平呈时间依赖性上升。结论：甲状腺激素缺乏会导致大鼠海马CAMK4及EGR3表达降低，从而抑制神经元树突的发育，表明CAMK4-EGR3信号轴可能在CH大鼠海马神经发育异常中发挥重要作用。
Abstract:
Objective：This stndy aims to investigate the effect of CAMK4-EGR3 signaling axis on neuronal dendritic development in the hippocampus of congenital hypothyroidism（CH） rats. Methods：The CH models were established in 1-day-old，7-day-old and 21-day-old SD rats，and were divided into CH group and control group. Transcriptome sequencing，q-PCR and Western blot were used to detect the expression of CAMK4 and EGR3，and immunofluorescence was used to observe the growth of neuronal dendrites. Results：①The protein expressions of CAMK4 and EGR3 in the hippocampus of the control group increased in a time dependent manner，and the expression of CH group was significantly lower than that of the control group（P < 0.05）；②After CAMK4 was knocked down in the primary hippocampal neurons，the expression of Egr3 was decreased correspondently，and the mean length of dendrites of hippocampal neurons was decreased compared with the control group；③After T3 stimulation on CH primary hippocampal neurons，the protein expression level of CAMK4 increased in a time dependent manner. Conclusion：Thyroid hormone deficiency can decrease the expression of CAMK4 and EGR3 in the hippocampus of rats，and inhibit the development of neuronal dendrites，suggesting that the CAMK4-EGR3 signaling axis plays an important role in the neurodevelopmental abnormalities in the hippocampus of CH rats.
