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

In our previous study, low-intensity pulsed ultrasound stimulation (LIPUS), a novel noninvasive neuromodulation tool, effectively alleviated depression-like behaviors in a rat model of depression. However, the underlying mechanisms remain unclear. The present study aimed to elucidate the relevant mechanisms through transcriptomic research. To induce depression-like phenotypes, rats were subjected to chronic unpredictable stress (CUS) for six weeks. Following this initial stress period, LIPUS was administered daily for an additional four weeks while the rats were continuously exposed to CUS, which was previously determined to significantly reduce immobility time in forced swimming test. The transcriptome expression profiles in the hippocampus and prefrontal cortex (PFC) were subsequently analyzed by RNA sequencing techniques. Overall, LIPUS reversed the abnormal expression of genes in the brain of model rats, especially the expression of genes linked to glucose and lipid metabolism. Specifically, we found that the CUS rats exhibited 3464 differentially expressed genes (DEGs) in the hippocampus and 1781 DEGs in the PFC compared to the control group. LIPUS reversed 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 PCR. The significant changes in the expression of hemoglobin subunit beta, growth hormone 1, and glucokinase were confirmed. The results suggest that LIPUS may alleviate depression-related manifestations by regulating cerebral oxygenation and sugar metabolism processes in the brain.