Background and Purpose: Alzheimer’s disease (AD) is associated with extensive cognitive impairment and increased tau protein phosphorylation in the hippocampus, which directly affect memory performance. Given that both aerobic exercise and niacin supplementation have shown potential neuroprotective effects in previous studies, investigating their role in modulating AD-induced damage is of great importance. Therefore, the present study aimed to evaluate the individual and combined effects of moderate-intensity aerobic exercise and niacin supplementation on improving memory and reducing tau phosphorylation in a streptozotocin (STZ)-induced AD rat model, to determine which intervention or combination thereof is more effective in mitigating cognitive deficits associated with this disease.
Materials and Methods: In this experimental study, 30 adult male Wistar rats (250±10 g) were randomly divided into five groups (n=6) after an acclimatization period under controlled environmental conditions: Control, AD, AD + Niacin, AD + Exercise, and AD + Combined. The AD model was induced via intracerebroventricular injection of streptozotocin (STZ) under standard stereotaxic and anesthetic conditions. In the intervention groups, moderate-intensity aerobic training was performed on a motorized treadmill for 4 weeks with a gradual increase in intensity. Niacin supplementation was administered via oral gavage at a dose of 100 mg/kg/day for 30 days. To evaluate cognitive performance, the Novel Object Recognition (NOR) test was used to assess short-term and long-term memory, and the T-maze test was used to measure working memory. Following behavioral testing, the expression levels of amyloid-beta (Aβ) and phosphorylated tau (AT8) proteins in the hippocampal tissue were quantified using Western blotting. Data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey's post hoc test, with the significance level set at P<0.05.
Results: STZ injection caused a significant decrease in the discrimination index of short- and long-term memory compared to the control group (P<0.001). In short-term memory, the combined group showed a significant increase in memory performance compared to the AD group (P<0.05). In long-term memory, the AD + Exercise (P<0.05) and AD + Combined (P<0.001) groups exhibited significant improvements compared to the AD group. In the T-maze test, the alternation percentage in the AD group significantly decreased compared to the control (P<0.0001); however, this rate significantly increased in the AD + Niacin (P<0.05), AD + Exercise (P<0.01), and AD + Combined (P<0.001) groups. In molecular assessments, the expression level of Aβ protein in the hippocampus of the AD group significantly increased compared to the control group (P<0.001). Conversely, Aβ levels significantly decreased in the AD + Niacin (P<0.05), AD + Exercise (P<0.05), and AD + Combined (P<0.01) groups compared to the AD group. Furthermore, the level of AT8 in the hippocampus of the AD group significantly increased (P<0.0001), while a significant decrease was observed in the AD + Niacin (P<0.001), AD + Exercise (P<0.001), and AD + Combined (P<0.0001) groups compared to the AD group. Notably, in the AD + Combined group, no significant difference was observed in the expression levels of Aβ and AT8 proteins compared to the healthy control group.
Conclusion: Moderate-intensity aerobic exercise and niacin supplementation, particularly when used in combination, significantly improve cognitive performance and reduce Aβ expression and tau protein phosphorylation in the hippocampus of STZ-induced AD rat models. These results indicate the protective and enhancing role of these interventions in mitigating cognitive impairments associated with Alzheimer's disease and may provide novel strategies for the prevention or treatment of this condition.