Abstract
The objective of this study was to investigate effects of metformin on body weight, blood glucose levels, glucose transporter (GLUT1), interleukin 1 β (IL-1β) and protein kinase B expression, antioxidant enzymes, expression of synaptic molecules, biomarkers of oxidative stress, lipid peroxidation, membrane fluidity and acetylcholinesterase (AChE) in diabetic aging brain of female rats. Male Wistar rats, young (3 months) adult (12 months) and aged (24 months) were diabetic by using alloxan monohydrate. Metformin was administered i.p. at a dose of 200mg/kg/day for 30 days to both control and diabetic aging rats. A detailed study was carried on expression of inflammatory cytokines, insulin receptor pathology and synapse, GLUT 1, biomarkers of oxidative stress and AChE activity. Present study shows that there was a similar pattern of increased expression of interleukin, protein kinase B, lipid peroxidation, blood glucose, insulin receptor expression and RNS levels with AChE activity, and a decrease in membrane fluidity, antioxidant enzymes activity and (GLUT1) expression in brain of both aging and diabetes. On the other hand, metformin treated groups exhibited significant reduction in helped to reverse the age related changes studied, to normal levels. Metformin treatments improved attention and memory functions with enhanced the levels of synaptic molecules synaptophysin and synapsin I. Our data showed that exogenous administration of metformin brought these changes to near normalcy in diabetic aging female rats. The results illuminate mechanisms of neuroprotection by metformin, and applying new strategies for control of neurodegenerative diseases including metabolic syndrome and Alzheimer’s disease.
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