Sex-specific neurobehavioural outcomes and brain stimulation pattern in adult offspring paternally exposed to methamphetamine
Sex-specific neurobehavioural outcomes and brain stimulation pattern in adult offspring paternally exposed to methamphetamine
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父亲接触甲基苯丙胺的成年后代的性别特异性神经行为结果和脑刺激模式
DOI：
10.1111/adb.13175
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发表时间：
2022-05-01
影响因子：
3.4
通讯作者：
Guan, Xiaowei
中科院分区：
文献类型：
--
作者：
Fan, Yu;Li, Zhaosu;Guan, Xiaowei
父亲接触甲基苯丙胺（甲基安非他明）会导致具有性别差异的后代出现长期行为缺陷。在这里，我们的目的是研究在受孕前暴露于甲基安非他明的第一代后代小鼠（F1小鼠）的性别特异性神经行为结果，并探索潜在的大脑机制。我们发现，父亲接触甲基安非他明仅在雌性F1小鼠中增加了焦虑样行为和空间记忆缺陷，而在后代中引起抑郁样行为，没有性别特异性差异。同时，meth诱导的F1小鼠在轻度刺激（室温水中3分钟）下表现出性别特异性的脑活动模式。总体而言，父亲接触甲基安非他明导致雄性和雌性F1小鼠的前边缘皮质（PrL）、边缘下皮质（IL）和伏隔核（NAc）核心钝化现象，这表明在轻度刺激下c-Fos水平下降。值得注意的是，在轻度刺激下，雄性F1小鼠杏仁核中央核（CeA）的活性被触发，而雌性F1小鼠的眶额皮质（OFC）、扣带皮质（Cg1）、NAc壳、内侧束（mHb）、海马背侧CA1 （dCA1）和海马腹侧CA1 （vCA1）神经元仅被钝化。综上所述，雄性和雌性F1小鼠之间不同的脑刺激模式可能有助于父亲暴露于甲基安非他明后的性别特异性行为结果，这表明在治疗父亲暴露于甲基安非他明的后代时应考虑性别差异。
Paternal methamphetamine (METH) exposure results in long-term behavioural deficits in the sub-generations with a sex difference. Here, we aim to investigate the sex-specific neurobehavioural outcomes in the first-generation offspring mice (F1 mice) paternally exposed to METH prior to conception and explore the underlying brain mechanisms. We found that paternal METH exposure increased anxiety-like behaviours and spatial memory deficits only in female F1 mice and caused depression-like behaviours in the offspring without sex-specific differences. In parallel, METH-sired F1 mice exhibited sex-specific brain activity pattern in response to mild stimulus (in water at room temperature for 3 min). Overall, paternal METH exposure caused a blunting phenomenon of prelimbic cortex (PrL), infralimbic cortex (IL) and nucleus accumbens (NAc) core in both male and female F1 mice, as indicated by the decreased c-Fos levels under mild stimulus. Of note, the activity of central nucleus of the amygdala (CeA) by mild stimulus was triggered in male but suppressed in female F1 mice, whereas the neurons of orbitofrontal cortex (OFC), cingulate cortex (Cg1), NAc shell, medial habenula (mHb), dorsal hippocampal CA1 (dCA1) and ventral hippocampal CA1 (vCA1) were only blunted in female F1 mice. Taken together, the distinct brain stimulation patterns between male and female F1 mice might contribute to the sex-specific behavioural outcomes by paternal METH exposure, which indicate that sex differences should be considered in the treatment of offspring paternally exposed drugs.