| 余樱
，石昭坤
，徐丹
，张兆辉
，汪晖.大鼠孕期尼古丁暴露致成年雌性子代抑郁症
易感机制研究[J].神经损伤功能重建,2018,13(6):271-275 |
| 大鼠孕期尼古丁暴露致成年雌性子代抑郁症
易感机制研究 |
| Study on the Mechanism of Increased Susceptibility to Depression in Adult Female RatsOffspring Resulting from Prenatal Nicotine Exposure |
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| DOI： |
| 中文关键词: 孕期尼古丁暴露 子代 抑郁症 前额叶皮质 突触 |
| 英文关键词: prenatal nicotine exposure offspring depression prefrontal cortex synapse |
| 基金项目:国家自然科学基金
（No. 81300984） |
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| 摘要点击次数: 2674 |
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| 中文摘要: |
| 目的：探讨大鼠孕期尼古丁暴露（PNE）致成年雌性子代抑郁症易感的宫内发生机制。方法：将受孕
Wistar大鼠随机分为对照组和PNE组，PNE组大鼠于孕9～20 d皮下注射尼古丁2 mg/(kg·d)，2次/日。部分
子代大鼠于孕20 d取脑切片NeuN免疫荧光染色观察前额叶皮质和海马形态改变；部分大鼠正常出生喂养
至3月龄，给予慢性不可预见性温和刺激（CUMS），检测刺激前后雌性子代大鼠行为学改变，实时定量PCR
检测前额叶皮质和海马组织中与突触生长发育相关基因的表达。结果：与对照组相比，旷场试验中PNE组
成年雌性子代大鼠 CUMS 后表现为总路程、总速率和直立次数明显减少（P＜0.05），粪便粒数增加（P＜
0.05），强迫游泳实验中不动时间明显延长（P＜0.01），表现出抑郁行为；PNE组孕20 d胎鼠前额叶皮质变薄，
海马细胞层结构不清，轴突不连续；CUMS后PNE组成年子代前额叶皮质和海马，突触生长发育相关基因
NR1、NR2A、NR2B、Syn I和Snap25 mRNA转录水平明显下降（P＜0.01）。结论：PNE导致大鼠成年雌性子
代应激后抑郁症易感性增加，可能与子代前额皮质和海马神经元和突触形成发育等基因转录水平降低，所
致前额叶皮质和海马结构和功能改变有关。 |
| 英文摘要: |
| To investigate the possible intrauterine mechanism of increased susceptibility of
depression in adult female rats offspring resulting from prenatal nicotine exposure (PNE). Methods: Pregnant
Wistar rats were randomly divided into control and PNE groups. PNE rats were given nicotine (2 mg/kg·d) by
subcutaneous injection from the 9th day to the 20th day of gestation. Brain sections were taken of some offspring
rats on the 20th day of pregnancy, and NeuN staining was performed to observe morphological changes in the
prefrontal cortex and hippocampus. The other offspring rats were raised to 3 months old and given chronic
unpredictable mild stimulation (CUMS). The behavioral changes of female offspring rats were observed before
and after stimulation. Real-time quantitative PCR was used to detect expression of genes related to synapse
formation in the prefrontal cortex and hippocampus. Results: Compared with the control group, the female rats
in the PNE group showed significant decrease in total distance traveled and total rate after CUMS in the
open-field test (P<0.05). The frequency of upright position decreased also (P<0.05). However, the quantity of
feces was increased in the PNE group (P<0.05). In the forced swimming test, adult female offspring in the PNE
group showed significantly longer immobility time than those in the control group (P<0.01), displaying
depressive behavior. Fetal offspring in the PNE group showed thinner prefrontal cortex and unclear cell layers in
the hippocampus with incomplete axons. The mRNA expression of NR1, NR2A, NR2B, Syn I, and Snap25 in the
prefrontal cortex and hippocampus was significantly decreased after CUMS in adult offspring of the PNE group
compared to those of the control group (P<0.01). Conclusion: Exposure to nicotine during pregnancy in rats
leads to an increased susceptibility to depression in their adult female offspring, which may be related to
decreased expression of genes involved in the development of neurons and synapses in the prefrontal cortex and
hippocampus, resulting in changes in the structure and function of the prefrontal cortex and hippocampus |
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