期刊
ACS CHEMICAL NEUROSCIENCE
卷 13, 期 5, 页码 648-663出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.1c00800
关键词
autism spectrum disorder; cerebral cortex; proteomics; valproic acid
资金
- National Natural Science Foundation of China [31870825]
- Shenzhen Bureau of Science, Technology and Information [JCYJ20170412110026229]
- Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions [2021SHIBS0003]
The study identified 79 differentially expressed proteins in the cerebral cortex of VPA rat model, mainly enriched at synapses and involved in energy metabolism, thyroid hormone synthesis pathway, and cytoskeleton. The dysregulation of these proteins may contribute to autism-like behavior in rats, as well as being associated with neuropsychiatric disorders. Increased expression of proteins related to energy metabolism suggests ASD may involve mitochondrial dysfunction that requires further investigation.
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.
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