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

Subclinical hypothyroidism in pregnant rats impaired learning and memory of their offspring by promoting the p75(NTR) signal pathway.
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妊娠大鼠亚临床甲状腺功能减退症通过促进 p75(NTR) 信号通路损害后代的学习和记忆

DOI:
10.1530/ec-18-0069
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发表时间:
2018-05
影响因子:
2.9
通讯作者:
Teng W
Teng W
中科院分区:
医学3区
文献类型:
--
作者:
Zhang F;Chen J;Lin X;Peng S;Yu X;Shan Z;Teng W

文献摘要

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母亲在怀孕期间甲状腺功能减退会影响其后代的神经发育。本研究旨在探讨亚临床甲状腺功能减退症(subclinical hypothyroidism,SCH)对子代空间学习记忆的影响及其与脑皮质凋亡因子的关系。雌性成年Wistar大鼠随机分为对照组(CON)、SCH组和明显甲减组(OH),每组15只。采用长时程增强(LTP)和Morris水迷宫(MWM)实验评价仔鼠的空间学习记忆能力。Western blotting检测p75神经营养因子受体(p75 NTR)、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。与CON组相比,SCH组和OH组的MWM中的逃逸潜伏期延长,LTP测试中的场兴奋性突触后电位降低。与CON组相比,SCH组和OH组大鼠大脑皮质p75 NTR、p-JNK、p53和Bax表达水平均升高。母亲在怀孕期间的SCH可能会损害后代的空间学习和记忆,并可能与大脑皮层细胞凋亡的增加。
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. Female adult Wistar rats were randomly divided into three groups (n = 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 (p75NTR), phospho-c-Jun N-terminal kinase (p-JNK), the pro-apoptotic protein p53 and Bax were detected by Western blotting. 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. p75NTR, 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. 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.