Abstract
Background and Objective: Type 1 diabetes is associated with widespread metabolic and neurological disturbances and may impair cognitive function through alterations in dopaminergic pathways, particularly in the hippocampus. Dopamine D2 receptor (DRD2) and tyrosine hydroxylase (TH) are key components of this pathway, and changes in their expression may reflect dysregulation of dopaminergic signaling. Despite existing evidence regarding the beneficial effects of physical activity on neuroplasticity and brain function, the effect of high-intensity interval training (HIIT) on molecular markers of the dopaminergic system under type 1 diabetic conditions has not been fully elucidated. Therefore, the present study aimed to investigate the effect of eight weeks of HIIT on the gene expression of dopamine D2 receptor and TH in the hippocampus of diabetic male Wistar rats.
Materials and Methods: This was an experimental study. Thirty-two male Wistar rats aged 6–8 weeks were randomly assigned to four groups: healthy control, sham, diabetic control, and diabetic + HIIT. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) at a dose of 50 mg/kg. The HIIT protocol was performed on a treadmill for 8 weeks, 5 sessions per week, at an intensity of 80% VO2max. Twenty-four hours after the last training session, hippocampal tissue was collected, and the gene expression levels of DRD2 and TH were measured using real-time RT-PCR. Data were analyzed using one-way analysis of variance followed by Tukey’s post hoc test at a significance level of P < 0.05 using SPSS version 26.
Results: At baseline, no significant difference was observed among the groups in blood glucose levels (P = 0.076). After 8 weeks, blood glucose levels in both diabetic groups were significantly higher than those in the healthy groups (P < 0.001), and HIIT did not produce a significant reduction compared with the sedentary diabetic group. DRD2 gene expression differed significantly among the groups (P = 0.014). This marker showed a significant decrease in the diabetic group compared with the healthy control group (P = 0.049), whereas a significant increase was observed in the diabetic + HIIT group compared with the diabetic group (P = 0.035). TH gene expression also differed significantly among the groups (P < 0.001). This marker was significantly higher in the diabetic group than in the healthy control group (P = 0.010), and it was also higher in the diabetic + HIIT group than in the healthy control group (P < 0.001); however, the difference between the two diabetic groups was not significant (P = 0.17).
Conclusion: Eight weeks of HIIT attenuated the diabetes-induced reduction in dopamine D2 receptor gene expression in the hippocampus of diabetic male Wistar rats, but did not significantly normalize the increased expression of tyrosine hydroxylase. These findings suggest that HIIT may improve certain aspects of hippocampal dopaminergic dysfunction under diabetic conditions, although its effects were not uniform across all components of this pathway.