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Abstract: We studied the effect of repeated exposure to dexamethasone (Dex) treatment on rat brain mitochondrial oxidative energy metabolism in developing rats at different postnatal ages, i.e. 2–5 week and in adults. The animals were injected with a dose of 2mg of Dex/kg body weight at around 7:00 a.m. for three alternative days prior to the day of sacrifice; the control group animals received saline vehicle. We measured rates of respiration with different substrates, viz. glutamate, pyruvate+malate, succinate and ascorbate+TMPD; the contents of individual cytochromes and the dehydrogenases and ATPase activities. Dex treatment, in general, stimulated the state 3 rates of respiration rates in young animals in age-dependent and substrate-specific manner except for the 3 week group, whereas in the adults there was substantial inhibition of the respiration. The pattern of dehydrogenases activities matched with respiration rates. Dex treatment also resulted in uncoupling of the second and third site of phosphorylation in 3-week-old animals and in the adults. The contents of cytochrome aa 3, b and ATPase activities decreased significantly after Dex treatment in all the age groups. The results thus emphasize that exposure to repeated Dex treatment can significantly influence the oxidative energy metabolism of brain mitochondria in young growing animals as well as in adults. [Copyright &y& Elsevier]

Abstract: Effects of treatment with dehydroepiandrosterone (DHEA) (0.2 or 1.0mg/kg body weight for 7 days) on oxidative energy metabolism in cerebral mitochondria from developing and young adult rats were examined. Treatment with DHEA did not change the body weight of developing rats but resulted in increase in the brain weight in 5 week group. In young adult rats the body weight increased following treatment with 1.0mg DHEA. State 3 and state 4 respiration rates with all the substrates increased following DHEA treatment, the effect being more pronounced in the developing rats. State 4 respiration rates were stimulated to variable extents. Contents of cytochromes aa 3 and b increased following DHEA treatment and once again the effect was more pronounced in the developing rats. DHEA treatment marginally changed the content of cytochromes c + c 1. In the developing rats the ATPase activity and the levels of dehydrogenases increased significantly by DHEA treatment. Results of our studies have shown that treatment with exogenous DHEA accelerates the process of maturation of cerebral mitochondria thus emphasizing the role of DHEA in brain development in postnatal life. [Copyright &y& Elsevier]

Abstract: The content of the neurosteroids, dehydroepiandrosterone (DHEA) in the brain decreases with aging. Also the oxidative energy metabolism is known to decrease with aging. Hence we examined the effects of treatment with DHEA (0.2 or 1.0mg/kg body weight for 7 days) on oxidative energy metabolism in brain mitochondria from old and young adult rats. State 3 respiration rates in brain mitochondria from old animals were considerably lower than those in young adults. Treatment with DHEA stimulated state 3 and state 4 respiration rates in both the groups of the animals in a dose-dependent manner. In the old rats following DHEA treatment, the state 3 respiration rates became comparable to or increased beyond those of untreated young adults. In contrast to the old rats, stimulatory effect of DHEA treatment was of greater magnitude in the young adults. However, at higher dose (1.0mg) the effect declined. Cytochrome aa 3 content in the brain mitochondria from old rats was significantly low but the content of cytochrome b was unchanged while the content of cytochromes c + c 1 had increased. Treatment with DHEA increased the content of cytochrome aa 3 and b in old as well as in young adult animals. Higher dose of DHEA (1.0mg) had adverse effect on the content of cytochrome c + c 1 . DHEA treatment stimulated ATPase activity in a dose-dependent manner in young adult rats whereas in the old rats the effect on ATPase activity was marginal. Dehydrogenases activities were somewhat lower in the old rats. DHEA treatment stimulated mitochondrial dehydrogenases activities in both the groups. Results of our studies suggest that judicious use of DHEA treatment can improve oxidative energy metabolism parameters in brain mitochondria from young adult as well as old rats. [Copyright &y& Elsevier]

Abstract: Early and late effects of alloxan-diabetes of lipid/phospholipid composition of rat brain microsomes and mitochondria were examined. In microsomes, early as well as late diabetic stages resulted in decrease in contents of total phospholipids (TPL) and increase in cholesterol (CHL). Insulin treatment restored TPL with further increase in CHL in 1 week group. In early diabetic stage there was increase in the sphingomyelin (SPM) while phosphatidylinositol (PI) and phosphatidylserine (PS) components decreased. Insulin treatment restored SPM and decreased the lysophospholipids (Lyso), PI, PS and phosphatidic acid (PA); phosphatidylethanolamine (PE) increased. In 1 month diabetic group phosphatidylcholine (PC) decreased while PI, PS and PE increased. Insulin treatment lowered the Lyso, SPM, PI, PS and PA while PC and PE increased. In mitochondria, at early stage of diabetes both CHL and TPL contents decreased; insulin treatment restored the former component. Late diabetic stage had no effect on CHL and TPL contents; insulin treatment brought about reduction in both. Diabetic state had marginal effect on phospholipid composition at both the stages. Insulin treatment had a generalized effect of lowering of PI and PS components and increasing diphosphatidylglycerol (DPG). The fluidity of microsomal membranes decreased progressively in the diabetic condition; insulin treatment fluidized the membrane at early stage. The fluidity of mitochondrial membranes increased in early diabetic stage and the effect was accentuated by insulin treatment. However, at the late stage the effects on membrane fluidity were marginal. [Copyright &y& Elsevier]

Abstract: Effects of STZ diabetes and treatment with insulin on cerebral mitochondrial metabolism in the male and female rats were examined. Diabetic state resulted in generalized decrease in the state 3 respiration rates in the males with practically all the substrates except glutamate where the opposite effect was seen. Diabetic state had no adverse effect on the respiratory activity in the females. Insulin treatment had no restorative effect in the males. By contrast in the females, adverse effects were noted. The cytochromes contents decreased in STZ diabetes with the effect being more pronounced in the males; treatment with 1 unit of insulin restored the cytochromes contents. STZ diabetes also resulted in decreased dehydrogenases activities with the effect being more pronounced in the females: insulin treatment resulted in hyper-stimulation of glutamate dehydrogenase and succinate DCIP reductase activities; restoration of malate dehydrogenase activity was only partial. The results point out that STZ diabetes and insulin treatments differentially affect cerebral mitochondrial energy metabolism in the male and female rats. [Copyright &y& Elsevier]