Data_Sheet_1_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刺激剂，对公共健康产生了重大影响。孕期及产后甲基苯丙胺暴露会改变后代基因表达、大脑发育和行为，尽管其潜在机制尚未完全明了。为评估这些对后代的不利影响，我们采用了一种孕期及产后甲基苯丙胺暴露的鼠标模型。对幼鼠进行了开放场、新物体识别、Y型迷宫和强迫游泳等行为学测试。此外，通过RNA测序技术，我们探讨了前额叶皮层基因表达的潜在变化。研究发现，暴露于甲基苯丙胺的鼠标表现出活动减少和认知能力受损。此外，还发现了参与神经递质传递、突触可塑性和神经炎症相关基因的差异表达，其中多巴胺信号通路发生了显著变化。这些数据表明，甲基苯丙胺暴露导致的行为变化可能存在潜在的神经和分子机制。涉及多巴胺信号传递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靶点。