The Role of CGRP Inhibition and High-Intensity Interval Training (HIIT) on Mtorc2 and VEGF Gene Expression in The Hippocampal Tissues of Male Wistar Rats

Abstract

Background The hippocampus, as one of the most critical regions of the brain, is significantly affected by exercise. The primary purpose of this study is to evaluate the effect of six weeks of high-intensity interval training (HIIT) and inhibition of calcitonin gene-related peptide (CGRP) on gene expression of vascular endothelial growth factor (VEGF) and serine/threonine type 2 kinase protein (mTORC2) in hippocampal tissue of male Wistar rats. Methods Thirty-two healthy male Wistar rats (8 weeks of age) were randomly assigned to one of four groups: control, CGRP inhibition, HIIT+CGRP inhibition, or HIIT. The CGRP inhibition group received 0.25 mg/kg/day of antibody intraperitoneally. The animals in the training groups underwent high-intensity interval training (HIIT, ten 2-minute work bouts per day at 22 m/min interspersed by 2-minute rest periods, five days/week). Real-time PCR (2-ΔΔCT) and one-way ANOVA were employed to measure the expression of genes and analyze the data, respectively. Results HIIT significantly enhanced VEGF (p≤0.002) and mTORC2 (p≤0.006) gene expression in the hippocampal tissue compared to the control group. HIIT+CGRP inhibition resulted in a substantial increase in VEGF expression compared to the control group (p≤0.007). While HIIT+CGRP inhibition significantly lowered mTORC2 gene expression (p≤0.001), HIIT alone did not (p≤0.001). Conclusions HIIT-induced physiological alterations in the hippocampus can improve the brain’s functional status via upregulation of VEGF and mTORC2 gene expression as an effective non-pharmacological method. Additionally, HIIT+CGRP inhibition may represent a new approach via the VEGF and mTORC2 pathways in the hippocampus.