Effect of a combined program of running exercise and environmental enrichment on memory function and neurogenesis markers in amyloid-beta-induced Alzheimer-like model.

Objectives: It is urgent to develop non-pharmacological interventions or multifactor combination approaches to combat Alzheimer's disease (AD). The effect of exercise (EX) combined with environmental enrichment (EE) on behavioral phenotypes and neurogenesis markers in an Alzheimer-like rat model was investigated. Materials and Methods: The groups consisted of AD, sham-operated, AD+EX, AD+EE, and AD+EX+EE. AD was produced by injection of amyloid-beta (1-42, 6 µg) intrahippocampally, and a daily treadmill for 3 consecutive weeks was used for EX animals. EE was a large cage (50× 50× 50 cm) containing differently shaped objects. Spatial learning and memory were evaluated in the Morris water maze (MWM), and a shuttle box was used to evaluate inhibitory avoidance memory. RT-PCR was performed to assess the expression of early neurogenesis markers, DCX, and Sox2 within the hippocampus. Results: Pretreatment with exercise and EE, both individually and in combination, could provide protection from memory impairments in AD rats. Combined treatment led to a significantly more pronounced improvement in memory deficits of AD rats than either paradigm alone. Combination therapy with exercise and EE could also reverse the passive avoidance memory impairment and hippocampal DCX expression of AD rats to the control levels. Conclusion: These data suggest that exercise in combination with cognitive engagement can provide a non-pharmacological and multidomain policy that may prevent or delay AD symptoms.