Transcriptomic Alterations in the Hippocampus and Prefrontal Cortex of Chronic Unpredictable Stress Rats Induced by Low-Intensity Pulsed Ultrasound.

Abstract

Abstract Neuromodulation techniques have shown promise in the treatment of depression. In our previous study, we demonstrated that low-intensity pulsed ultrasound stimulation (LIPUS), a novel noninvasive neuromodulation tool, effectively ameliorated depression-like behaviors in a rat model of depression. However, the underlying mechanisms of its therapeutic effect remain unclear. The present study aims to elucidate the relevant mechanisms through transcriptomic research. To induce depression-like phenotypes, rats were subjected to chronic unpredictable stress (CUS) for six weeks. Throughout these six weeks, LIPUS was administered daily to the CUS rats, utilizing a pulse repetition frequency of 200 Hz. The transcriptome expression profiles in the hippocampus and prefrontal cortex (PFC) were subsequently analyzed by RNA sequencing techniques. We found that the CUS rats exhibited 3,464 differentially expressed genes (DEGs) in the hippocampus and 1,781 DEGs in the PFC when compared to the control group. Ultrasound stimulation was able to reverse the expression of 592 genes in the hippocampus and 254 genes in the PFC. Functional analysis revealed a significant enrichment of DEGs related to oxygen carrier activity and sugar metabolism. Subsequently, the alterations in the top ten genes were validated using real-time quantitative polymerase chain reaction. The significant changes in the expression of hemoglobin subunit beta, growth hormone 1, and glucokinase were confirmed. The results suggest that LIPUS may ameliorate depression-related manifestations by regulating cerebral oxygenation and sugar metabolism processes in the brain.