Transcriptome profile analysis of genes by RNA-sequencing in neonatal maternal separation rats with autistic-like...

Autism spectrum disorder (ASD) is a neurodevelopmental disorder marked by repetitive behaviors and difficulties in social interaction and communication. The pathogenesis of ASD remains poorly understood, and no definitive treatment is currently available. This study aimed to systematically identify key genes and signaling pathways involved in autistic-like behaviors by performing genome-wide transcriptional profiling on a neonatal maternal separation (NMS) rat model, thereby revealing the underlying molecular mechanisms.

In this study, genome-wide transcriptional profiling of male Sprague-Dawley rats subjected to NMS, one of the animal models of ASD, was conducted via RNA sequencing (RNA-seq). The transcriptomic data were systematically analyzed to identify the key genes and pathways that are involved in autistic-like behaviors.

Rats subjected to NMS exhibited autism-like behaviors. The RNA-seq data were derived from total RNA collected from both control (CON) and NMS rats. In the NMS group, there were 202 differentially expressed genes (DEGs) compared to the CON group, with 128 genes upregulated and 74 downregulated according to an adjusted P value of less than 0.05 as determined by DESeq software. Gene Ontology (GO) enrichment analysis revealed that the upregulated DEGs were most enriched in serotonergic synapse, transcription factor AP-1 complex, DNA-binding transcription factor activity, RNA polymerase, transcription regulatory region sequence-specific, tissue development, and response to xenobiotic stimulus. Conversely, the downregulated DEGs were primarily enriched in synapse, dendrite, neuron projection, postsynaptic membrane, axon terminus, neuropeptide binding, enkephalin receptor activity, oxidoreductase activity, oleamide hydrolase activity, anandamide amidohydrolase activity, amidase activity, nervous system development, neuron development, generation of neurons, neuron differentiation, neuron projection development, neurogenesis, and regulation of cell communication. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the prominently enriched pathways included neuroactive ligand-receptor interaction, cAMP signaling pathway, PI3K/Akt signaling pathway, AGE/RAGE signaling pathway in diabetic complications, maturity onset diabetes of the young, estrogen signaling pathway, Th1 and Th2 cell differentiation, Th17 cell differentiation, and antigen processing and presentation. Gene interaction analysis identified 15 key central genes, including Jun, Fos, Smad3, Runx2, Klf4, Fosb, Atf3, Fn1, Ngfr, Egr2, Tagln, Ntrk1, Nos3, Gli1, and Notch3.

This study examined the alterations in global gene expression in NMS rats and systematically identified the key genes and signaling pathways in rats subjected to NMS. These findings provide insights into the complex molecular mechanisms involved in autism-like behaviors and lay the groundwork for future ASD research. The study's sequence data have been archived in the Sequence Read Archive (https://dataview.ncbi.nlm.nih.gov/object/PRJNA1275822?reviewer=skc0d219fusapt07bptheggsdu).