Data_Sheet_2_Prenatal and postnatal methamphetamine exposure alters prefrontal cortical gene expression and behavior in mice.PDF

Methamphetamine is a highly abused psychostimulant that substantially impacts public health. Prenatal and postnatal methamphetamine exposure alters gene expression, brain development, and behavior in the offspring, although the underlying mechanisms are not fully defined. To assess these adverse outcomes in the offspring, we employed a mouse model of prenatal and postnatal methamphetamine exposure. Juvenile offspring were behaviorally assessed on the open field, novel object recognition, Y-maze, and forced swim tests. In addition, RNA sequencing was used to explore potential alterations in prefrontal cortical gene expression. We found that methamphetamine-exposed mice exhibited decreased locomotor activity and impaired cognitive performance. In addition, differential expression of genes involved in neurotransmission, synaptic plasticity, and neuroinflammation were found with notable changes in dopaminergic signaling pathways. These data suggest potential neural and molecular mechanisms underlying methamphetamine-exposed behavioral changes. The altered expression of genes involved in dopaminergic signaling and synaptic plasticity highlights potential targets for therapeutic interventions for substance abuse disorders and related psychiatric complications.

甲基苯丙胺是一种被广泛滥用的精神兴奋剂，对公共健康产生了重大影响。孕期及产后暴露于甲基苯丙胺会改变后代基因表达、脑部发育和行为，尽管其潜在机制尚未完全阐明。为评估这些对后代的不良影响，我们采用了孕期及产后甲基苯丙胺暴露的鼠类模型。对幼鼠进行开放场地、新物体识别、Y迷宫和强迫游泳测试等行为学评估。此外，通过RNA测序技术，我们探究了前额叶皮质基因表达中可能发生的改变。我们发现，暴露于甲基苯丙胺的鼠类表现出活动量减少和认知功能损害。此外，在神经递质传递、突触可塑性和神经炎症相关基因的差异表达中，发现多巴胺信号通路发生显著变化。这些数据表明，甲基苯丙胺暴露导致的行为改变可能存在潜在的神经和分子机制。涉及多巴胺信号传导和突触可塑性的基因表达改变，突显了治疗物质滥用障碍及其相关精神并发症的潜在治疗靶点。