scholarly journals 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

Author(s):  
Iman Mohseni ◽  
Maghsoud Peeri ◽  
Mohammad Ali Azarbayjani

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 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 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 (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 Aβ 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 Conclusion: In the present study, behavioral and biochemical analysis demonstrated that aerobic training and donepezil hydrochloride treatment for 4 weeks protect Aβ-injected male rats against memory impairment.

2019 ◽  
Vol 32 (3) ◽  
pp. 152-163 ◽  
Author(s):  
Li Lin ◽  
Sarmad Sheraz Jadoon ◽  
Shang-Zhi Liu ◽  
Ru-Yi Zhang ◽  
Fan Li ◽  
...  

Background: Alzheimer disease (AD) is the most common type of dementia which is becoming a primary problem in the present society, but it lacks effective treatment methods and means of AD. Tanshinone IIA (Tan IIA) has been reported to have neuroprotective effects to restrain the Aβ25 -35-mediated apoptosis. However, few studies try to understand how Aβ1-42 affects hyperphosphorylation of tau and how Tan IIA regulates this process at the molecular level. Methods: Fifty male Sprague-Dawley rats were randomly divided into 5 groups and infused through the lateral ventricle with Aβ1-42 except the control group. Then the rats were treated with Tan IIA through intragastric administration for 4 weeks. After the ability of learning and memory being measured, histomorphological examination and Western blot were used to detect the possible mechanism in the AD-associated model rats. Results: We observed that Aβ1-42 infusion could induce spatial learning and memory deficits in rats. Simultaneously, Aβ1-42 also could reduce the neuron in cornu ammonis 1 and dentate gyrus of hippocampus, as well as increase the levels of cleaved caspase 3, hyperphosphorylated tau at the sites Ser396, Ser404, and Thr205 with enhancing staining of black granules in brain. We also found that Aβ1-42 could increase the activity of extracellular signal-regulated protein kinase (ERK) and glycogen synthase kinase-3β (GSK-3β). Meanwhile, these phenomena could be ameliorated when Tan IIA was used. Conclusion: We concluded that Tan IIA might have neuroprotective effect and improving learning and memory ability to be a viable candidate in AD therapy with mechanisms involving the ERK and GSK-3β signal pathway.


Author(s):  
Siros Hosseini Askarabadi ◽  
Rahim Mirnasouri ◽  
Masoud Rahmati

Introdution: Neuropathic pain is one of the most important factors affecting the quality of life of people with diabetes mellitus; regular exercises may have a role in reducing the pain associated with diabetes. The purpose of this study was the effect of six weeks aerobic training on environmental neuropathic pain and expression of the NOTCH1 pathway in the spinal cord of diabetic male rats. Methods: 40 male Wistar rats (age: 8 weeks old; weight 220-250g) were randomly divided into 4 groups: diabetic neuropathy training (DNT), diabetic neuropathy control (DNC), healthy training (HT) and healthy control (HC).The diabetic groups were induced by intraperitoneal injection of streptozotocin (STZ) and two weeks after induction of diabetes, behavioral pain tests were administered and endurance training protocol was performed for 6 weeks and 5 sessions per week. .The data were analyzed via  SPSS software version 19 and one-way ANOVA with a significant level (P <0.05) Results: After 6 weeks of aerobic training, the expression of NOTCH1 HES1 and il6 genes in diabetic neuropathy training group was significantly lower than the diabetic neuropathy control group (P≤0/05). The mean weight of the diabetic neuropathic training group was more than the diabetic neuropathy control group (p=0/001). Also, exercise significantly decreased blood glucose levels in the diabetic neuropathy group (P=0/237). Conclusion: It seems that aerobic exercise on rats with diabetic neuropathy can affect on pain sensation as well as the levels of NOTCH1, HES1 and il6 factors, and aerobic exercise is a suitable method for preventing, controlling and treating pain associated with diabetes.


2011 ◽  
Vol 32 (1) ◽  
pp. 67-72 ◽  
Author(s):  
Koichiro Mori ◽  
Yutaro Obara ◽  
Takahiro Moriya ◽  
Satoshi Inatomi ◽  
Norimichi Nakahata

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