DEHYDROEPIANDROSTERONE MODULATES MEMBRANE FUNCTIONS, ANTIOXIDANT ENZYMES, AND BEHAVIORAL CHANGES IN BRAIN OF AGING FEMALE RATS

Abstract

Dehydroepiandrosterone (DHEA), one of the major steroid hormones, and its ester have recently received attention with regard to aging and age-related diseases like Alzheimer 's disease. These changes increase during aging when the level of DHEA is decreased. DHEA is synthesized de novo in the brain and its substantial fall with age has been shown to be associated with neuronal vulnerability to neurotoxicity processes. The objective of this study was to observe the changes in activity of acetylcholinesterase, antioxidant enzymes (superoxide dismutase, glutathione S-transferase) genomic DNA degradation, membrane fluidity, lipid peroxidation levels and neurolipofuscin accumulation occurring in aging male rat brain, and to see whether these changes are restored to normal levels after exogenous administration of DHEA. The aged male rats (4, 14 and 24 months age group) were given subcutaneous injection of DHEA (30 mg/kg/day for 1 month). Learning was tested in a Morris water maze and ultrastructural studies of brain region by MRI. The results obtained in the present work revealed that normal aging was associated with significant increases in genomic DNA degradation, lipid peroxidation levels and neurolipofuscin accumulation in the brains 4, 14 and 24 months age group male rats, and a decrease in acetylcholinesterase and antioxidant enzymes activities and membrane fluidity. Ultrastructural studies of the frontal cortex of exposed rats revealed that the changes were more pronounced in the aged treated rats in terms of presence of neurolipofuscin, vacuolization and lysosomal degradation. Administration of DHEA brought these changes to near normalcy. It can therefore be suggested that DHEA's beneficial effects seemed to arise from its antioxidant, antilipofuscin, antilipidperoxidative effects, implying a therapeutic potential drug for age related changes.