Background: Alzheimer's disease (AD) represents the most prevalent form of dementia, characterized by memory loss, and is a complex, progressive neurodegenerative condition. Objectives: This study aimed to explore the impact of aerobic interval training (AIT) combined with Ginkgo biloba (GB) supplementation on passive avoidance memory function and the expression of the glial cell-derived neurotrophic factor (GDNF) gene in rats afflicted with AD. Methods: A total of forty-four male Wistar rats, each weighing approximately 250 ± 20 g, were maintained in a controlled environment at a specified temperature. Over 8 weeks (5 days per week), they underwent AIT and received GB supplements at a dosage of 100 mg/kg. The rats were randomly assigned into six groups: Healthy control (HC) with 7 rats, AD control (AC) with 8 rats, amyloid-β (Aβ) injection plus GB supplement (Aβ + GB) with 8 rats, Aβ injection plus GB supplement plus AIT (Aβ + GB + AIT) with 8 rats, Aβ injection plus AIT (Aβ + AIT) with 8 rats, and sham surgery (SS) with 5 rats. The shuttlebox apparatus was utilized to assess the effect of Aβ on passive avoidance memory and to confirm disease induction. GDNF gene expression was measured using the qRT-PCR method. Results: The study found significant improvements in passive avoidance memory in the Aβ + AIT and Aβ + GB + AIT groups compared to the AC group after 8 weeks of AIT and GB supplementation (P = 0.02 and P = 0.000, respectively). Long-term memory performance was notably enhanced in the Aβ + GB + AIT group (P = 0.000). Additionally, GDNF expression significantly increased in the Aβ + GB + AIT and Aβ + GB groups in comparison to the AC group (P = 0.000 and P = 0.01, respectively). Conclusions: A synergistic effect of AIT and GB supplementation was observed, leading to an increase in GDNF gene expression and improvements in both passive avoidance memory and long-term memory in male rats with AD.
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