en بیولوژی سلولی- مولکولی Cellular and Molecular Biology پژوهشي Original Research <strong>Background</strong>: Accumulation of amyloid-&beta; (A&szlig;) 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 A&szlig;-injected male rats.<br> <strong>Objectives</strong>: 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 A&szlig;-injected male rats.<br> Methods: Male Rats were injected with an A&beta; solution into their CA1 hippocampal region. After 20 days, the rats were treated with donepezil hydrochloride at doses of 2 mg/kg/d by gavage and following treadmill exercise for 4 weeks. Then, after 24 h, they performed the Morris water maze test for five days. Additionally, we studied the molecular factors involved in neuronal plasticity, such as Ca2+/cAMP-response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) on day 33. The animals were also evaluated histologically to determine the deposition of A&beta; in the brain tissue.<br> <strong>Results</strong>: Behavioral analysis showed that in the probe test, the latency to the platform zone significantly increased in the training group (F1,20=6.815; P<0.05) and in the drug group (F1,20=6.369; P<0.05). But there were no significant changes in the combined group compared with the control group (F1,20=3.909; P>0.05). Molecular analysis showed that CREB gene expression improved in the training group (F1,8=9893.539; P<0.01) and in the drug group (F1,8=631.958; P<0.01). But in the combined group, there were no significant changes compared with the A&beta; group (F1,8=2.556; P>0.05). BDNF gene expression improved in the training group (F1,8=25.077; P<0.001), and in the drug group (F1,8=45.296; P<0.001). Also, in the combined group, this change was significant compared with the control group (F1,8=64.342; P<0.001). Histomorphometric analysis showed that the density of survived neurons was considerably increased in the combined group (P<0.01), and the drug group (P<0.05) compared to the control group<br> <strong>Conclusion</strong>: In the present study, behavioral and biochemical analysis demonstrated that aerobic training and donepezil hydrochloride treatment for 4 weeks protect A&beta;-injected male rats against memory impairment. Alzheimer disease, Donepezil hydrochloride, Hippocampus, Treadmill running 181 190 http://pbr.mazums.ac.ir/browse.php?a_code=A-10-779-1&slc_lang=en&sid=1 Iman Mohseni mohseniiman@yahoo.com 10031947532846005838 10031947532846005838 No Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran. Maghsoud Peeri m.peeri@iauctb.ac.ir 10031947532846005839 10031947532846005839 Yes Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran. Mohammad Ali Azarbayjani Ali.azarbayjani@gmail.com 10031947532846005840 10031947532846005840 No Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.