Impact of Gestational Haloperidol Exposure on miR-137-3p and Nr3c1 mRNA Expression in Hippocampus of Offspring Mice.
Impact of Gestational Haloperidol Exposure on miR-137-3p and Nr3c1 mRNA Expression in Hippocampus of Offspring Mice.
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DOI：
10.1093/ijnp/pyac044
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发表时间：
2022-10-25
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精神分裂症是一种由环境和遗传因素引起的精神障碍。产前暴露于抗精神病药物（胎儿大脑的一个环境因素）会诱导后代发生细胞凋亡神经变性和认知障碍，类似于精神分裂症。目的是研究氟哌啶醇（HAL）暴露的胎儿海马的分子生物学变化的RNA表达作为一个模型的障碍。妊娠小鼠给予HAL（1 mg/kg/d）。通过RNA测序研究子代海马中上调和下调的基因表达，并通过qPCR方法进行验证，并通过计算机分析预测微RNA（miR）调节mRNA表达的变化。体外实验使用双荧光素酶测定来鉴定miRNA。RNA测序分析显示HAL组与对照组相比有显著的基因表达变化（1370个上调和1260个下调基因）（P <0.05和q < 0.05）。其中，Nr 3c 1 mRNA表达的增加被成功验证，并且计算机分析预测microRNA-137- 3 p（miR-137- 3 p）可能调节该基因的表达。子代海马miR-137- 3 p的表达在第1代显著降低，而在第2代显著升高。Neuro 2a细胞的体外实验表明，miR-137- 3 p负调控Nr 3c 1 mRNA表达，HAL组上调。这些发现将是了解抗精神病药物对胎儿大脑的分子生物学影响的关键。
Schizophrenia is a mental disorder caused by both environmental and genetic factors. Prenatal exposure to antipsychotics, an environmental factor for the fetal brain, induces apoptotic neurodegeneration and cognitive impairment of offspring similar to schizophrenia. The aim was to investigate molecular biological changes in the fetal hippocampus exposed to haloperidol (HAL) by RNA expression as a model of the disorder. HAL (1 mg/kg/d) was administered to pregnant mice. Upregulated and downregulated gene expressions in the hippocampus of offspring were studied with RNA-sequencing and validated with the qPCR method, and micro-RNA (miR) regulating mRNA expressional changes was predicted by in silico analysis. An in vitro experiment was used to identify the miRNA using a dual-luciferase assay. There were significant gene expressional changes (1370 upregulated and 1260 downregulated genes) in the HAL group compared with the control group on RNA-sequencing analysis (P < .05 and q < 0.05). Of them, the increase of Nr3c1 mRNA expression was successfully validated, and in silico analysis predicted that microRNA-137-3p (miR-137-3p) possibly regulates that gene’s expression. The expression of miR-137-3p in the hippocampus of offspring was significantly decreased in the first generation, but it increased in the second generation. In vitro experiments with Neuro2a cells showed that miR-137-3p inversely regulated Nr3c1 mRNA expression, which was upregulated in the HAL group. These findings will be key for understanding the impact of the molecular biological effects of antipsychotics on the fetal brain.
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影响因子：
15.1
作者：
Glass, Ruthy;Norton, Sara;Kusnecov, Alexander W.
通讯作者：
Kusnecov, Alexander W.
影响因子：
3.1
作者：
Hasan, Alkomiet;Falkai, Peter;Moeller, Hans-Juergen
通讯作者：
Moeller, Hans-Juergen
影响因子：
2.5
作者：
Japanese Society of Neuropsychopharmacology
通讯作者：
Japanese Society of Neuropsychopharmacology
影响因子：
4.5
作者：
Gomes, Felipe, V;Zhu, Xiyu;Grace, Anthony A.
通讯作者：
Grace, Anthony A.
DOI：
10.1093/bioinformatics/btp101
发表时间：
2009-04-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Bindea G;Mlecnik B;Hackl H;Charoentong P;Tosolini M;Kirilovsky A;Fridman WH;Pagès F;Trajanoski Z;Galon J
通讯作者：
Galon J