EFFECTS OF AGING AND 17B-ESTRADIOL ON GLUCOSE TRANSPORTER (GLUT3) AND MEMBRANE FUNCTIONS IN FEMALE RAT BRAIN: A THERAPEUTIC POTENTIAL DRUG FOR ALZHEIMER’S DISEASE

Abstract

Recently, there has been a growing interest in the action and functions of the ovarian steroid hormone estradiol, particularly on whether they are neuroprotective for such age related disease and neurodegenerative conditions like stroke, Parkinson's disease and Alzheimer's disease. The objective of this study was to observe the changes in activities of mitochondrial enzymes (monoamine oxidase (MAO), Na+K+ATPase and Ca2+ATPase), membrane fluidity, DNA degradation, and glucose transporter 4 (GLUT3) expression in brains of female Wistar rats of 3 months (young), 12 months (adult) and 24 months (old) age groups, and to see whether these changes are restored to normal levels after exogenous administration of 17β-estradiol (E2) (0.1 μg/gm body weight for one month). Controls animals received an equal volume of vehicle. After 30 days of hormone treatment, experimental animals of all the groups were sacrificed and brains were isolated for further study. Whole brains were rapidly excised, and washed with chilled normal saline. Tissue homogenates (1:10) were prepared in homogenizing buffer containing 0.25 M sucrose 0.02 M triethanolamine (pH 7.4) and 0.12 mM dithiothreitol. The pellet obtained after centrifugation at 12,000 rpm using SM 22 rotor on a high speed cooling centrifuge (SORVALL 5CA) containing crude synaptosomes (mitochondria and synaptosomes). The results obtained in the present work revealed that normal aging was associated with significant decrease in the activity of Na+K+ATPase, Ca2+ATPase and membrane fluidity, GLUT3 levels in the brains of aging female rats, and an increase in DNA degradation and MAO activity. The present study showed that estradiol treatment significantly decreased DNA degradation, and MAO activity in brain of aging rats, and a reversal of Na+K+ATPase, Ca2+ATPase and GLUT3 levels was achieved. It can therefore be concluded that estradiol's beneficial effects seemed to arise from its antilipofuscin, antioxidant, antilipidperoxidative effects, implying an overall anti-aging action. 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.