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孕鼠亚临床甲状腺功能减退通过促进p75信号通路损害其后代的学习和记忆。

Subclinical hypothyroidism in pregnant rats impaired learning and memory of their offspring by promoting the p75 signal pathway.

作者信息

Zhang Fan, Chen Jian, Lin Xinyue, Peng Shiqiao, Yu Xiaohui, Shan Zhongyan, Teng Weiping

机构信息

Department of Endocrinology and MetabolismInstitute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.

Department of Endocrinology and MetabolismInstitute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China

出版信息

Endocr Connect. 2018 May;7(5):688-697. doi: 10.1530/EC-18-0069. Epub 2018 Apr 18.

Abstract

OBJECTIVE

Maternal hypothyroidism during pregnancy can affect the neurodevelopment of their offspring. This study aimed to investigate the effects of maternal subclinical hypothyroidism (SCH) on spatial learning and memory, and its relationship with the apoptotic factors in cerebral cortex of the offspring.

METHODS

Female adult Wistar rats were randomly divided into three groups ( = 15 per group): control (CON) group, SCH group and overt hypothyroidism (OH) group. Spatial learning and memory in the offspring were evaluated by long-term potentiation (LTP) and Morris water-maze (MWM) test. The protein expression of the p75 neurotrophin receptor (p75), phospho-c-Jun N-terminal kinase (p-JNK), the pro-apoptotic protein p53 and Bax were detected by Western blotting.

RESULTS

The Pups in the SCH and OH groups showed longer escape latencies in the MWM and decreased field-excitatory post synaptic potentials in LTP tests compared with those in the CON group. p75, p-JNK, p53 and Bax expression levels in the cerebral cortex increased in pups in the SCH and OH groups compared with those in the CON group.

CONCLUSIONS

Maternal SCH during pregnancy may impair spatial learning and memory in the offspring and may be associated with the increased apoptosis in the cerebral cortex.

摘要

目的

孕期母体甲状腺功能减退会影响其后代的神经发育。本研究旨在探讨母体亚临床甲状腺功能减退(SCH)对后代空间学习和记忆的影响及其与后代大脑皮质凋亡因子的关系。

方法

将成年雌性Wistar大鼠随机分为三组(每组15只):对照组(CON)、SCH组和显性甲状腺功能减退(OH)组。通过长时程增强(LTP)和Morris水迷宫(MWM)试验评估后代的空间学习和记忆能力。采用蛋白质免疫印迹法检测p75神经营养因子受体(p75)、磷酸化c-Jun氨基末端激酶(p-JNK)、促凋亡蛋白p53和Bax的蛋白表达。

结果

与CON组相比,SCH组和OH组幼崽在MWM试验中的逃避潜伏期更长,在LTP试验中的场兴奋性突触后电位降低。与CON组相比,SCH组和OH组幼崽大脑皮质中p75、p-JNK、p53和Bax的表达水平升高。

结论

孕期母体SCH可能损害后代的空间学习和记忆能力,并可能与大脑皮质凋亡增加有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b5a/5952246/577c3bd9efbf/ec-7-688-g001.jpg

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