Transcriptomic Analysis of High-Intensity Interval Training in High-Fat-Diet-Induced Spontaneous Hypertensive Rats’ Brains

Hypertension contributes to brain dysfunction through apoptosis, oxidative stress, reduced neuronal connectivity, and neurotransmitter imbalance. Exercise training is a non-pharmacological strategy known to modulate these molecular alterations. This study investigated the effects of high-intensity interval training (HIIT) on transcriptomic changes in the cerebral cortex of spontaneously hypertensive rats (SHR) fed a high-fat diet (HFD). Rats were assigned to either a HIIT intervention group (HIIT-HFD-SHR) or a sedentary control group (HFD-SHR). Cortical RNA was extracted, sequenced using the Illumina NovaSeq 6000 platform, and analyzed with DESeq2. Functional enrichment was conducted using Metascape. RNA-seq identified 1223 differentially expressed genes (DEGs) (adjusted <i>p</i> < 0.05), with 51 remaining significant under stringent criteria (adjusted <i>p</i> < 0.001, |log₂FC| > 0.5). Among these, eight key genes were closely associated with the regulation of apoptosis and autophagy, including seven downregulated (<i>Egr1</i>, <i>Atf3</i>, <i>Tgm2</i>, <i>Lgals1</i>, <i>Nr4a1</i>, <i>Plekhf1</i>, <i>Nupr1</i>) and one upregulated (<i>Trim39</i>). This transcriptomic analysis following HIIT also modulated circadian rhythm, long-term memory processes, and hypoxia response in the hypertensive brain. These findings indicate that HIIT decreases apoptosis and autophagy and improves circadian rhythm, long-term memory, and hypoxia in hypertensive rats' brains.