Objective: The objective of this study was to investigate effects of metformin on glucose transporter (GLUT1, GLUT3) expression, intracellular calcium levels, expression of synaptic molecules synaptophysin and synapsin I, biomarkers of oxidative stress such as antioxidant capacity (FRAP), malondialdehyde (MDA), reduced glutathione (GSH), protein carbonyl (PCO), reactive oxygen species (ROS) and neurolipofuscin in diabetic aging brain of female rats.

Background: The emerging view is that diabetic brain features many symptoms that are best described as accelerated brain aging. Metformin is the most frequently used oral anti-diabetic drug, which apart from hypoglycaemic activity, improves serum lipid profiles, positively influences the process of haemostasis, and possesses anti-inflammatory properties.

Methods: Young (3 months) adult (12 months) and aged (24 months) rats will be diabetic by using alloxan monohydrate. Metformin was administered i.p. at a dose of 200 mg/kg/day for 30 days to both control and diabetic aging rats. A detailed study was carried on expression of glucose transporter, calcium levels, biomarkers of oxidative stress. Morris water maze with expression of synaptic molecules synaptophysin and synapsin I and ultrastructural studies of brain region by magnetic resonance imaging.

Results: Present study shows that there was a similar pattern of increased intracellular calcium levels, neurolipofuscin, MDA, PCO, and ROS levels, and a decrease in levels of FRAP , GSH and (GLUT1, GLUT3) 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.

Conclusions: The results of this study will be useful for pharmacological modification of the aging process and applying new strategies for control of age related disorders including metabolic syndrome and neurodegenerative diseases.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/role-of-metformin-in-diabetic-aging-female-rat-brain-a-future-therapy-for-neurodegenerative-diseases/