iTRAQ-Based Proteomics Analysis of Rat Cerebral Cortex Exposed to Valproic Acid before Delivery

Abstract

Autism spectrum disorder (ASD) is a neurological and developmental disorder characterized by social and communication difficulties. Valproic acid (VPA) injection during pregnancy elicits autism-like behavior in the offspring, making it a classic animal model of ASD. However, the mechanisms involved have not yet been determined. In this study, we used iTRAQ (isobaric tags for relative and absolute quantification) proteomics analysis of the cerebral cortex of a VPA rat model (VPA group) and controls (CON group). The results showed that 79 differentially expressed proteins (DEPs) were identified between the VPA group and the CON group. Based on bioinformatics analysis, the DEPs were mainly enriched at synapses, especially glutamatergic synapses and GABAergic synapses. Some DEPs were involved in energy metabolism, thyroid hormone synthesis pathway, and Na + -K + -ATPase. Cytoskeleton and endoplasmic reticulum (ER) stress-related proteins were also involved. Some DEPs matched either the ASD gene database or previous reports on cerebral cortical transcriptome studies in VPA rat models. Dysregulation of these DEPs in the cerebral cortex of VPA rats may be responsible for autism-like behavior in rats. We also found that some DEPs were associated with neuropsychiatric disorders, implying that these diseases share common signaling pathways and mechanisms. Moreover, increased expression of DEPs was associated with energy metabolism in the cerebral cortex of VPA rats, implying that ASD may be a distinct type of mitochondrial dysfunction that requires further investigation.

Continuous high-frequency deep brain stimulation of the anterior insula modulates autism-like behavior in a valproic acid-induced rat model

“…A study found that Htt -KO mice exhibited autism-like behavioral characteristics like Fmr1 -KO mice and that the mitochondrial fusion phenotype could be rescued by enhancing the Htt expression [ 74 ]. The present study found a decreased HTT in the AI of VPA rats, which is congruent to the findings of an earlier study [ 75 ]. The results suggested that the downregulation of HTT may lead to abnormal behavior in VPA-exposed rats.…”

Pathophysiological Studies of Monoaminergic Neurotransmission Systems in Valproic Acid-Induced Model of Autism Spectrum Disorder

“…Altered gene expression profiles in neural development and function, cellular development and function, cell death, and immune system are also detected in the amygdala of maternally VPA-treated offspring brains [54]. Proteomics study has further found changes in protein expression profiles in synaptic function, energy metabolism, cytoskeleton and neuropsychiatric disorders in the cerebral cortex of maternally VPA-treated rat offspring [55]. Note that molecular and cellular changes in the VPA-induced animal models are similar, but not identical to those in idiopathic ASD patients.…”

Proteomic Study on the Mechanism of Arsenic Neurotoxicity in the Rat Cerebral Cortex and the Protective Mechanism of Dictyophora Polysaccharides against Arsenic Neurotoxicity

“…CIAPIN1 (1:500), TBCD (1:1000), and FXN (1:1000) were probed by corresponding primary antibodies, followed by incubation with horseradish peroxidase (HRP)-conjugated secondary antibodies (1:5000) (anti-rat or anti-rabbit, Abmart, Shanghai, China). Enhanced chemiluminescence (ECL) detection reagents were used to visualize the immunoreactive bands, which were then analyzed with the Tanon-5200 chemiluminescent imaging system (Tanon Science and Technology, China) …”

“…Enhanced chemiluminescence (ECL) detection reagents were used to visualize the immunoreactive bands, which were then analyzed with the Tanon-5200 chemiluminescent imaging system (Tanon Science and Technology, China). 100 5.7. Statistical Analysis.…”