Autism spectrum disorders (ASDs) are increasingly being diagnosed. Hypotheses link ASD to genetic, epigenetic, or environmental factors. The role of oxidative stress and the imbalance between excitatory and inhibitory neurotransmission in the pathogenesis of ASD has been suggested. Rats in which ASD symptoms are induced by valproate (VPA) or thalidomide (THAL) application in utero are useful models in ASD studies. Our study investigated whether rats in ASD models show changes in metabolite levels in the brain consistent with the hypothetical pathomechanisms of ASD. Female rats were fed one dose of 800 mg/kg VPA or 500 mg/kg THAL orally on the 11th day of gestation, and 1-month offspring were used for the experiments. Metabolic profiles from proton nuclear magnetic resonance spectroscopy of hydrophilic and hydrophobic extracts of rat hippocampi were subjected to OPLS-DA statistical analysis. Large differences between both models in the content of several metabolites in the rat hippocampus were noticed. The following metabolic pathways were identified as being disturbed in both ASD models: steroid hormone biosynthesis; fatty acid biosynthesis; the synthesis and degradation of ketone bodies; glycerophospholipid metabolism; cholesterol metabolism; purine metabolism; arginine and proline metabolism; valine, leucine, and isoleucine biosynthesis and degradation. These results indicate disorders of energy metabolism, altered structure of cell membranes, changes in neurotransmission, and the induction of oxidative stress in the hippocampus. Our data, consistent with hypotheses of ASD pathomechanisms, may be useful in future ASD studies, especially for the interpretation of the results of metabolomics analysis of body fluids in rat ASD models.

自闭症谱系障碍（ASD）越来越多地被诊断出来。假设将ASD与遗传，表观遗传或环境因素联系起来。已经提出氧化应激的作用以及兴奋性和抑制性神经传递之间的失衡在ASD的发病机理中的作用。在子宫内应用丙戊酸盐（VPA）或沙利度胺（THAL）诱发ASD症状的大鼠是ASD研究中的有用模型。我们的研究调查了ASD模型中的大鼠是否显示出与ASD假设的致病机理相符的大脑中代谢物水平的变化。在妊娠的第11天，给雌性大鼠口服800mg / kg V​​PA或500mg / kg THAL一剂，并将1个月的后代用于实验。对大鼠海马的亲水和疏水提取物的质子核磁共振光谱的代谢谱进行OPLS-DA统计分析。两种模型之间在大鼠海马中几种代谢物的含量上存在很大差异。在两个ASD模型中，以下代谢途径均被确定为受干扰：类固醇激素的生物合成；脂肪酸生物合成 酮体的合成和降解；甘油磷脂代谢；胆固醇代谢 嘌呤代谢；精氨酸和脯氨酸代谢；缬氨酸，亮氨酸和异亮氨酸的生物合成和降解。这些结果表明能量代谢紊乱，细胞膜结构改变，神经传递改变以及海马中氧化应激的诱导。我们的数据