Autism spectrum disorder (ASD) is characterized by deficits in communication and social interaction, restricted interests, and stereotyped behavior. Environmental factors, such as prenatal exposure to valproic acid (VPA), may contribute to the increased risk of ASD. Since disturbed functioning of the purinergic signaling system has been associated with the onset of ASD and used as a potential therapeutic target for ASD in both clinical and preclinical studies, we analyzed the effects of suramin, a non-selective purinergic antagonist, on behavioral, molecular and immunological in an animal model of autism induced by prenatal exposure to VPA. Treatment with suramin (20 mg/kg, intraperitoneal) restored sociability in the three-chamber apparatus and decreased anxiety measured by elevated plus maze apparatus, but had no impact on decreased reciprocal social interactions or higher nociceptive threshold in VPA rats. Suramin treatment did not affect VPA-induced upregulation of P2X4 and P2Y2 receptor expression in the hippocampus, and P2X4 receptor expression in the medial prefrontal cortex, but normalized an increased level of interleukin 6 (IL-6). Our results suggest an important role of purinergic signaling modulation in behavioral, molecular, and immunological aberrations described in VPA model, and indicate that the purinergic signaling system might be a potential target for pharmacotherapy in preclinical studies of ASD.

中文翻译：

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在丙戊酸诱发的自闭症动物模型中，单剂量抗嘌呤能疗法对行为和分子改变的影响。

自闭症谱系障碍（ASD）的特征是沟通和社交互动不足，兴趣受限和刻板行为。产前暴露于丙戊酸（VPA）等环境因素可能会导致ASD风险增加。由于嘌呤能信号传导系统的功能紊乱与ASD的发作有关，并且在临床和临床前研究中均被用作ASD的潜在治疗靶标，因此我们分析了非选择性嘌呤能拮抗剂suramin对行为，分子和神经元的影响。产前暴露于VPA诱发的自闭症动物模型中的免疫和免疫学作用。苏拉明（20 mg / kg，腹膜内）治疗可恢复三腔仪的社交能力，并通过高架迷宫仪测得的焦虑降低，但对VPA大鼠的社交互动减少或伤害阈值较高没有影响。苏拉明治疗不影响VPA诱导的海马P2X4和P2Y2受体表达以及内侧前额叶皮层中P2X4受体表达的上调，但使白介素6（IL-6）的水平升高正常化。我们的结果表明，嘌呤能信号传导调节在VPA模型中描述的行为，分子和免疫学畸变中具有重要作用，并表明嘌呤能信号传导系统可能是ASD临床前研究中药物治疗的潜在目标。P2X4受体和P2X4受体在内侧前额叶皮层中的表达，但使白介素6（IL-6）的水平升高正常化。我们的结果表明，嘌呤能信号传导调节在VPA模型中描述的行为，分子和免疫学畸变中具有重要作用，并表明嘌呤能信号传导系统可能是ASD临床前研究中药物治疗的潜在目标。P2X4受体和P2X4受体在内侧前额叶皮层中的表达，但使白介素6（IL-6）的水平升高正常化。我们的结果表明，嘌呤能信号传导调节在VPA模型中描述的行为，分子和免疫学畸变中具有重要作用，并表明嘌呤能信号传导系统可能是ASD临床前研究中药物治疗的潜在目标。