Sex-dependent effects of in utero cannabinoid exposure on cortical function.
Sex-dependent effects of in utero cannabinoid exposure on cortical function.
复制标题
DOI：
10.7554/elife.36234
复制
发表时间：
2018-09-11
期刊：
影响因子：
7.7
通讯作者：
Manzoni OJ
中科院分区：
文献类型：
--
作者：
Bara A;Manduca A;Bernabeu A;Borsoi M;Serviado M;Lassalle O;Murphy M;Wager-Miller J;Mackie K;Pelissier-Alicot AL;Trezza V;Manzoni OJ
大麻素可以穿过胎盘，从而可能在神经发育过程中干扰胎儿内源性大麻素信号，导致长期的缺陷。尽管关于怀孕期间吸食大麻的报告越来越多，但产前大麻素暴露(PCE)的长期后果仍然不完全清楚。在这里，我们报告了怀孕期间暴露于低剂量大麻类药物的成年大鼠后代行为和神经元缺陷的性别差异。在男性中，PCE减少了社会互动，消融了内源性大麻样长期抑郁(LTD)，并增强了前额叶皮质锥体神经元的兴奋性，而女性则幸免于难。第1组mGluR和内源性大麻素信号调节情绪行为和突触可塑性。值得注意的是，PCE后的性别差异包括mGluR1/5和TRPV1R mRNA的水平。最后，mGlu5的正变构调节和AND水平的提高恢复了PCE成年男性的LTD和社会相互作用。总而言之，这些结果突出了PCE影响的显著性别差异，并提出了扭转PCE有害影响的策略。
Cannabinoids can cross the placenta, thus may interfere with fetal endocannabinoid signaling during neurodevelopment, causing long-lasting deficits. Despite increasing reports of cannabis consumption during pregnancy, the protracted consequences of prenatal cannabinoid exposure (PCE) remain incompletely understood. Here, we report sex-specific differences in behavioral and neuronal deficits in the adult progeny of rat dams exposed to low doses of cannabinoids during gestation. In males, PCE reduced social interaction, ablated endocannabinoid long-term depression (LTD) and heightened excitability of prefrontal cortex pyramidal neurons, while females were spared. Group 1 mGluR and endocannabinoid signaling regulate emotional behavior and synaptic plasticity. Notably, sex-differences following PCE included levels of mGluR1/5 and TRPV1R mRNA. Finally, positive allosteric modulation of mGlu5 and enhancement of anandamide levels restored LTD and social interaction in PCE adult males. Together, these results highlight marked sexual differences in the effects of PCE and introduce strategies for reversing detrimental effects of PCE.