Project description:Valproic acid (VPA) is a clinically used antiepileptic drug, but it has significant risks for low verbal intelligence quotient scores, attention deficit hyperactivity disorder and autism spectrum disorder in children when it is administered during pregnancy. Prenatal VPA exposure is reported to affect neurogenesis and neuronal migration and differentiation. In addition, growing evidence showed that a brain immune cell, microglia are activated by VPA treatment. However, a role of activated microglia by VPA remains unclear. The purpose of this study is identify a candidate gene which is responsible for VPA-induced behavioral disorders.
Project description:In this study, we explored molecular alterations in the hippocampus of prenatal valproic acid (VPA)-exposed rats as a model of autism spectrum disorders (ASD). In addition, we assessed effects of chronic administration of intranasal oxytocin, a promising peptide for ASD treatment. Comparative analyses revealed that prenatal VPA exposure altered gene expression, a part of which is involved in key features including memory, developmental process, and epilepsy. Oxytocin partly improved these gene expression, which were predicted to interact with those involved in social behaviors and hippocampal-dependent memory. The present study documented molecular profiling in the hippocampus related to ASD and improvement by chronic treatment of oxytocin.
Project description:Prenatal exposure to valproic acid (VPA), an antiepileptic and mood-stabilizing drug, is a well-established environmental risk factor for autism spectrum disorder (ASD). To investigate region-specific molecular alterations, we performed tandem mass tag (TMT)-based quantitative proteomic profiling of the striatum in 9–10 week-old mice prenatally exposed to VPA and control littermates. Striatal tissues were processed by protein extraction, digestion, TMT labeling, and high-pH reversed-phase fractionation, followed by LC–MS/MS analysis on a Q-Exactive HF-X mass spectrometer. In total, 101 differentially expressed proteins (47 upregulated, 54 downregulated) were identified. Functional enrichment analysis implicated pathways related to synaptic transmission, neuronal development, oxidative stress response, and excitation/inhibition balance. Key down-regulated proteins included parvalbumin (PVALB), NR2F1, and metallothioneins (MT1, MT2, MT3), highlighting disrupted inhibitory signaling and metal ion homeostasis in VPA-exposed mice. This dataset provides comprehensive proteomic profiles of striatal tissue, supporting molecular insights into the mechanisms by which prenatal VPA exposure contributes to ASD-related phenotypes.
Project description:Prenatal exposure to valproic acid induces sex-specific alterations in rat cortical and hippocampal neuronal structure and function in vitro
Project description:In this dataset we include the expression data obtained by dissected prefrontal cortical tissue from sprague-dawley rats exposed to saline or valproic acid on gestation day 12.5 in utero. This data was used to obtain prefrontal cortical genes to determine sex differences in a model of autism spectrum disorder.
Project description:DNA methylation profiling of CD34 positive cells derived from cord blood at birth following prenatal stress The groups consist of 8 individuals with low levels of prenatal stress (control) and 10 individuals with high levels of prenatal stress (stress)
Project description:Prenatal exposure to valproic acid, an established anti-epileptic drug, has been reported to impair postnatal cognitive function of children from epileptic mothers. Nevertheless, its pathology and proper treatment to minimize the effects remain unknown. In mice, we found that the postnatal cognitive function impairment was mainly caused by a reduction of adult neurogenesis and abnormal neuronal features in the hippocampus, which could be ameliorated by voluntary running. Pregnant mice received an oral administration of methylcellulose (MC), valproic acid (VPA) or valpromide (VPM) once a day on three consecutive embryonic days (E) 12.5, E13.5, and E14.5 and were sampled 3hr after the last administration (E14.5), at E18.5, and at 12 weeks of age.
Project description:Prenatal exposure to valproic acid, an established anti-epileptic drug, has been reported to impair postnatal cognitive function of children from epileptic mothers. Nevertheless, its pathology and proper treatment to minimize the effects remain unknown. In mice, we found that the postnatal cognitive function impairment was mainly caused by a reduction of adult neurogenesis and abnormal neuronal features in the hippocampus, which could be ameliorated by voluntary running.