Improvement of Learning and Memory Deficits With Aerobic Training and Donepezil Co-therapy in Amyloid-β beta-injected Male Rats Through the CREB and BDNF Signaling Pathway

Background: Accumulation of amyloid-β (Aß) plaques, primarily in the hippocampus, leads to neuronal death and Alzheimer disease. Exercise and medications can prevent and treat neuronal diseases. This study aimed to determine the effects of aerobic training and donepezil, a medication used in Alzheimer disease, on the improvement of learning and memory deficits in Aß-injected male rats. Objectives: This study aimed to determine the effects of aerobic training and donepezil, a medication used in Alzheimer disease, on the improvement of learning and memory deficits in Aß-injected male rats. Methods: Male Rats were injected with an Aβ solution into their CA۱ hippocampal region. After ۲۰ days, the rats were treated with donepezil hydrochloride at doses of ۲ mg/kg/d by gavage and following treadmill exercise for ۴ weeks. Then, after ۲۴ h, they performed the Morris water maze test for five days. Additionally, we studied the molecular factors involved in neuronal plasticity, such as Ca۲+/cAMP-response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) on day ۳۳. The animals were also evaluated histologically to determine the deposition of Aβ in the brain tissue. Results: Behavioral analysis showed that in the probe test, the latency to the platform zone significantly increased in the training group (F۱,۲۰=۶.۸۱۵; P<۰.۰۵) and in the drug group (F۱,۲۰=۶.۳۶۹; P<۰.۰۵). But there were no significant changes in the combined group compared with the control group (F۱,۲۰=۳.۹۰۹; P>۰.۰۵). Molecular analysis showed that CREB gene expression improved in the training group (F۱,۸=۹۸۹۳.۵۳۹; P<۰.۰۱) and in the drug group (F۱,۸=۶۳۱.۹۵۸; P<۰.۰۱). But in the combined group, there were no significant changes compared with the Aβ group (F۱,۸=۲.۵۵۶; P>۰.۰۵). BDNF gene expression improved in the training group (F۱,۸=۲۵.۰۷۷; P<۰.۰۰۱), and in the drug group (F۱,۸=۴۵.۲۹۶; P<۰.۰۰۱). Also, in the combined group, this change was significant compared with the control group (F۱,۸=۶۴.۳۴۲; P<۰.۰۰۱). Histomorphometric analysis showed that the density of survived neurons was considerably increased in the combined group (P<۰.۰۱), and the drug group (P<۰.۰۵) compared to the control group Conclusion: In the present study, behavioral and biochemical analysis demonstrated that aerobic training and donepezil hydrochloride treatment for ۴ weeks protect Aβ-injected male rats against memory impairment.

Keywords:

Alzheimer disease , Donepezil hydrochloride , Hippocampus , Treadmill running