Phenotypic Resemblance to Neuropsychiatric Disorder and Altered mRNA Profiles in Cortex and Hippocampus Underlying α Knockout.

Background: Previous studies of the functions of α have been limited to immune activities and skeletal muscle development. Immunological factors have been identified as one of the multiple causes of psychosis, and neurological symptoms have been described in α knockout (KO) mice. Seeking to explore possible mechanisms for this in the α mouse brain, we analyzed gene expression patterns in the cortex and hippocampus using the RNA-seq technique.

Methods: α KO mice were generated and littermate wildtype (WT) mice were used as a control group. A Y-maze was used to assess behavior differences between the two groups. The cortex and hippocampus of 3-month-old male mice were prepared and RNA-seq and transcriptome analysis were performed by gene set enrichment analysis (GSEA).

Results: Compared with the WT group, α KO animals showed higher speed in the novel arm and more entrance frequency in the old arm in the Y-maze experiment. GSEA indicated that 18 pathways were downregulated and 13 pathways upregulated in both cortex and hippocampus from the GO, KEGG, and Hallmark gene sets. The downregulated pathways formed three clusters: respiratory chain and electron transport, regulation of steroid process, and skeletal muscle development.

Conclusion: α KO mice exhibit altered expression of multiple pathways, which could affect many functions of the brain. Lipid biosynthesis and metabolism in the central nervous system (CNS) should be investigated to provide insights into the effect of α on psychosis in this murine model.