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Background and objective: Insulin and its receptor are located in the central nervous system where it regulates many important processes such as neural proliferation, apoptosis, synaptic transmission, neuronal survival, synaptic plasticity, learning and memory. Alzheimer's disease (AD) is characterized by the accumulation of extracellular amyloid-β (Aβ) plaques, and intracellular aggregation of hyperphosphorylated Tau protein. Currently there is widening recognition that AD is closely associated with impaired insulin signaling and glucose metabolism in brain, suggesting it to be a brain-specific form of diabetes and so also termed as "type 3 diabetes". Insulin has been shown to affect both Aβ levels and Tau phosphorylation. Experimental evidence suggests a link between type 2 diabetes and AD. Insulin modulates metabolism of beta-amyloid precursor protein (APP) in neurons, decreasing the intracellular accumulation of Aβ. Therefore investigating the role of agents that could improve neuronal insulin resistance merit attention in AD therapeutics. In present study, we aimed to investigate the therapeutic efficacy of intra ventricular injection of metformin on spatial learning and memory of streptozotocin(STZ) Rat Model of AD Materials and Methods: 48 Female wistar rate (200-250gr) were divided into 6 groups(n=6): control, STZ, STZ+Salin(5ul), STZ+Metformin(50,100,200ug/kg, i.c.v. for 10 day). For induction of AD, STZ (3 mg/kg, i.c.v, 10 μl each) were administered bilaterally into latral ventricles. All rates were tested spatial learning and memory in the Morris water maze. Results : We observed that pre-training microinjection of Metformin in to lateral ventricle for 10 day improves spatial learning and memory in STZ Rat Model of AD in a dose dependent manner, so that rats of these groups found platform in less time and with less distance traveled, in comparison with STZ+Salin group, in the radial maze. Conclusion: The results demonstrate possible therapeutic efficacy of metformin in AD by its ability to sensitize neuronal insulin resistance and also show that metformin is useful for AD treatment.

Keywords: Alzheimer\'s disease, Learning, Metformin, Spatial memory

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