Abstract
Introduction: Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders and is associated with cognitive decline, as well as metabolic, physiological, and behavioral alterations. Aerobic exercise can improve neural function and modulate certain physiological processes through enhancing brain plasticity and neuroprotective mechanisms. Likewise, Salvia officinalis (sage) possesses considerable neuroprotective potential due to its antioxidant and anti-inflammatory properties. Despite reports supporting the independent effects of these interventions, their combined effects have not yet been fully elucidated. Therefore, the aim of the present study was to investigate the physical, cognitive, and psychological effects of aerobic training and Salvia officinalis, administered individually and in combination, in a trimethyltin Chloride (TMT)-induced animal model of Alzheimer’s disease.
Methods: In this experimental study, 40 male rats aged 8–10 months and weighing 270–300 g were used. Following the induction of Alzheimer’s disease by a single intraperitoneal injection of trimethyltin Chloride (TMT(; 10 mg/kg) (1), the animals were randomly assigned to five groups: (1) TMT-induced Alzheimer’s disease model (TMT), (2) Sham group receiving the solvent (Sham), (3) TMT-induced model receiving Salvia officinalis extract (TMT+S), (4) TMT-induced model undergoing aerobic training (TMT+AT), and (5) TMT-induced model receiving a combination of aerobic training and Salvia officinalis extract (TMT+AT+S). In addition, eight healthy rats were assigned to a healthy control group (HC). The aerobic training protocol was performed for 8 weeks, 3 sessions per week, with each session lasting 15–48 minutes at a speed of 10–24 m/min on a motorized treadmill (2). The Salvia officinalis-treated groups received a daily intraperitoneal injection of ethanolic Salvia officinalis extract at a dose of 50 mg/kg for 8 weeks (3).At the end of the intervention period, Body Weight, brain weight, and hippocampal weight were measured as physiological and tissue-related indicators (1). In addition, the number of entries into the open arms and the time spent in the open arms were assessed as indices of anxiety-like behavior using the Elevated Plus Maze (EPM) test (1), while hanging time was evaluated as a behavioral index using the wire-hang test (3). Furthermore, maximal running speed was assessed as a physiological indicator used to determine exercise intensity and evaluate aerobic performance (2)

Results:In the TMT+AT, TMT+S, and TMT+AT+S groups, brain weight, hippocampal weight, number of entries into the open arm, time spent in the open arm, and wire hang holding time were significantly higher than those in the TMT group (P≤0.01). In the TMT+S group, body weight was significantly higher than in the TMT group (P=0.001). Moreover, in the combined intervention group (TMT+AT+S), time spent in the open arm and wire hang holding time were significantly greater than those in the TMT+S and TMT+AT groups (P=0.001). The number of entries into the open arm in the TMT+AT+S group was also significantly higher than that in the TMT+S group (P=0.001)
Conclusion:Aerobic training and Salvia officinalis, both individually and especially in combination, appear to improve physical indices and anxiety-like behaviors in a TMT-induced rat model of Alzheimer’s disease. The superiority of the combined intervention suggests possible complementary effects of exercise and sage and supports further investigation of this non-pharmacological approach in neurodegenerative models.