Background: Autism spectrum disorder (ASD) involves challenges in social interaction and communication and repetitive behaviours. CNTNAP4 is implicated in neuronal signalling, and its deficiency plays a role in ASD. Transcriptomic analyses revealed similar gene expression between the brain and in humans as well as in mice. However, the relationships between the brain and testicular gene expression profiles and metabolism in ASD remain unclear. In this study, the effects of Cntnap4 deletion on gene expression and metabolic profiles in the cerebral cortex and testes were investigated to better understand ASD pathogenesis.
Methods: Cntnap4 knockout mice were used to explore transcriptomic and metabolomic alterations. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were employed to identify significantly altered pathways.
Results: Cntnap4 deletion caused significant changes in both tissues. In the cerebral cortex, GO and KEGG analyses revealed differentially expressed genes (DEGs) related to mitochondrial energy production and synaptic signalling. Metabolomic analysis revealed altered levels of metabolites such as glutamic acid and glutamine. In the testes, 482 DEGs were linked to mitochondrial function and steroid biosynthesis. Additionally, commonly downregulated genes in both tissues highlighted disruptions in antioxidant activity and glutathione metabolism.
Conclusions: These findings suggest that Cntnap4 deletion impacts mitochondrial function, synaptic signalling, and metabolic processes, contributing to the ASD phenotype. By highlighting these mechanisms, this study provides insights into ASD pathogenesis and potential molecular targets for treatment and highlights the importance of the mitochondrial and synaptic pathways in the development of ASD associated with Cntnap4 deficiency.
Keywords: Autism spectrum disorder; Cerebral cortex; Cntnap4; Metabolomics; Testicles; Transcriptomics.
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