Indian Journal of Experimental Biology Vol. 46, December 2008, pp. 852-854 Na + K + -ATPase activity in response to exogenous dehydroepiandrosterone administration in aging rat brain Asia Taha, Monika Mishra, N Z Baquer & Deepak Sharma* School of Life Sciences, Jawaharlal Nehru University, New Delhi110 067, India Received 10 July 2008; revised 8 October 2008 Influence of exogenously administered dehydroepiand- rosterone (DHEA) on the activity of Na + K + ATPase was investigated in synaptosomal fraction from cerebral cortex, cerebellum, hippocampus and medulla regions of brain of 12 and 22 months old rats. DHEA was administered daily at the dose of 30 mg/kg/body wt, intraperitonially (ip) in both the age groups of rats for 1 month. Results showed that Na + K + ATPase activity, increased in DHEA treated rats in both the age groups. In terms of per cent increase, 22 months old animals showed significant increase in Na + K + ATPase activity in the synaptosomal fraction of all the four brain regions than in 12 months old DHEA-treated rats. This showed that exogenous DHEA modulated the activity of Na + K + ATPase and also protected the age-related loss of membrane integrity and functions. It was concluded that exogenous DHEA might be beneficial in terms of neuroprotection against age-related loss of Na + K + ATPase mediated brain functions like learning and memory. Keywords: Aging, Brain, Dehydroepiandrosterone, Na + K + -ATPase Sodium potassium adenosine triphosphatase (Na + K + ATPase) is known to be a key enzyme involved in maintenance of ionic gradient of Na + and K + ions, resting potential across the nerve cell membrane 1 and the maintenance of action potentials (nerve impulse) 2 . The enzyme activity has been shown to increase in the developing rat brain, while decreasing during normal ageing 5-9 . There are studies demonstrating age-related decline of spontaneous action potentials 3,4 and Na + K + ATPase activity in crude synaptosomal fraction from parietal cortex, hippocampus and striatum regions of brain 5 and have been shown to positively correlate with each other 8 . Therefore, ion-motive Na + , K + -ATPase is believed to be important for neuronal electrical activity and excitability and has been a parameter of interest in aging 6 . Dehydroepiandrosterone (DHEA), a precursor of corticosteroid hormones, though synthesized in the adrenal cortex, its level in brain is higher than in other organs, particularly in younger age groups, both in human and rodents. Gradual fall in DHEA levels with age correlates with a variety of neurological disorders, as the lower level of DHEA may leave the brain unprotected against neurotoxic challenges 10 . Enhanced neural and glial cell survival is reported in hippocampus after exposure to DHEA. DHEA also ameliorates the neurobiological alteration known to occur with age 11-12 . DHEA provides neuroprotection against oxidative stress induced by hyperglycaemia 13-15 , CCl 4 16 , CuSO 4 17 H 2 O 2 / FeSO 4 18 and in diabetic rats 19 . Mechanism of protective effect of DHEA on oxidative stress, excitotoxicity and apoptosis has been recently reported 20 . Since, DHEA has been shown to modulate the physiology and pathology of brain on many aspects such as learning, synaptic transmission, neurodegenerative diseases, emotions, stress and menstrual cycle linked disorders 21 and act as antianxiety and antidepressant 22 , it would be of great significance to investigate response of Na + K + ATPase to exogenous DHEA in understanding the effect of DHEA on the nerve cell membrane functions. Therefore, in the present study we investigated the Na + K + ATPase activity in cerebellum, cortex, hippocampus and medulla regions of aging rat brain and its treatment with exogenously administered DHEA. Chemicals⎯Ouabain, ATP and BSA were obtained from Sigma Aldrich Chemicals Co USA. All other chemicals were of analytical grade. Animals⎯Male Wistar rats of 12 and 22 month age groups (250-300g) were obtained from the central animal house facility of Jawaharlal Nehru University Delhi, The animals were housed at 22°±2° C under 0800 to 2000 h light and provided with food (commercial rat food pellets; Hindustan liver limited Delhi) and water ad libitum. Each rat was checked for health status by observing various criteria such as tail sores, posture hunch, grooming, nose red rim, eye red rim and tumors. The experimentation protocol was approved by the Institutional Animal Ethical Committee (IAEC), JNU New Delhi. DHEA administration⎯Experimental animals were administered DHEA, dissolved in dimethyl- __________________ *Correspondent author Telephone: 011-26704508 E-mail: deepak57in@yahoo.co.in