KIF17 mediates the learning and memory impairment in offspring induced by maternal exposure to propofol during middle pregnancy
KIF17 mediates the learning and memory impairment in offspring induced by maternal exposure to propofol during middle pregnancy
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KIF17介导孕中期母亲暴露于异丙酚所致后代学习记忆障碍
DOI：
10.3892/mmr.2018.8479
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
FOQUAN LUO
中科院分区：
文献类型：
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作者：
LIUQING WU;SHENGQIANG WANG;YUNLIN FENG;WEIHONG ZHAO;WEI ZUO;LIANG ZHONG;JIAMEI LIN;WEILU ZHAO;FOQUAN LUO
临床前研究表明，丙泊酚可能会对发育中的大脑造成神经元损伤。先前的一项研究表明，在大鼠模型中，母亲在妊娠早期或晚期暴露于丙泊酚会导致后代的学习和记忆障碍。然而，在中期妊娠期间暴露于丙泊酚是否会导致后代的长期行为缺陷仍有待阐明。N-甲基-D-天冬氨酸受体2B亚基（NR 2B）在记忆调节中起关键作用。为了发挥其功能，NR 2B必须通过驱动蛋白家族成员17（KIF 17）转运到神经元膜。本研究的目的是探讨KIF 17在孕中期暴露于丙泊酚引起的大鼠子代学习记忆障碍中的作用。孕鼠在妊娠第14天（G14）暴露于丙泊酚4和8 h，对照组孕鼠接受等体积的生理盐水。从出生后第30天（P30）至P36，采用Morris水迷宫测试评估后代的学习和记忆。采用免疫印迹法检测海马KIF 17蛋白、总NR 2B（T-NR 2B）和膜NR 2B（M-NR 2B）的表达。结果表明，丙泊酚暴露导致学习和记忆障碍，并降低海马中KIF 17和M-NR 2B蛋白水平;然而，没有观察到T-NR 2B表达的变化。这些结果表明，母体丙泊酚暴露在中期妊娠损害后代大鼠的学习和记忆，通过抑制KIF 17的表达和抑制NR 2B易位到神经元膜。
Preclinical studies suggest that propofol may cause neuronal injury to the developing brain. A previous study demonstrated that, in a rat model, maternal exposure to propofol during early or late pregnancy caused learning and memory impairment in the offspring. However, whether propofol exposure during middle pregnancy can cause long‑term behavioral deficits in the offspring remains to be elucidated. N‑methyl‑D‑aspartate receptor 2B subunit (NR2B) serves a critical role in memory modulation. To exert its function, NR2B must be transported to the neuronal membrane by kinesin family member 17 (KIF17). The aim of the present study was to investigate the role of KIF17 in learning and memory impairment in rat offspring caused by propofol exposure during middle pregnancy. Pregnant rats were exposed to propofol on gestational day 14 (G14) for 4 and 8 h, with control pregnant rats receiving an equal volume of normal saline. The learning and memory of the offspring was assessed using Morris water maze tests from postnatal day 30 (P30) to P36. The levels of KIF17 protein, total NR2B (T‑NR2B) and membrane NR2B (M‑NR2B) in the hippocampus were detected using western blotting. The results demonstrated that propofol exposure caused learning and memory deficits and decreased KIF17 and M‑NR2B protein levels in the hippocampus; however, no but changes in the expression of T‑NR2B were observed. These results indicate that maternal propofol exposure during middle pregnancy impairs learning and memory in offspring rats by suppressing the expression of KIF17 and inhibiting the translocation of NR2B to the neuronal membrane.