1574 The Journal of Maternal-Fetal and Neonatal Medicine, 2012; 25(9): 1574–1585 © 2012 Informa UK, Ltd. ISSN 1476-7058 print/ISSN 1476-4954 online DOI: 10.3109/14767058.2011.648235 Objective: The present study assesses the thrifty phenotype response of neonatal corticosterone programming to a diabe- togenic challenge in adult rats and the role of melatonin as a deprogrammer. Methods: Neonates of both sexes, born of healthy male and female rats maintained under standard conditions of temperature and light, were separated and, equal number of pups was assigned to lactating mothers. Pups treated with either saline or corticosterone or, a combination of corticosterone and melatonin from postnatal day (PND) 2 to PND 14 and, at 120 days of age, six animals from each treat- ment group were rendered diabetic by alloxanization. Various serum and tissue parameters pertaining to glycaemic regula- tion, dyslipidemia, hepatic and renal distress and oxidative stress were analysed in adult rats of all groups. Results: The results indicate compromised feed efficiency, hyperglycaemia, hypoinsulinemia, decreased glycogen content, elevated serum and tissue lipids and serum markers of hepatic and renal stress, together with increased lipid peroxidation, and decreased levels of non-enzymatic and enzymatic antioxidants in corticosterone programmed diabetic animals than in the non-programmed diabetic rats. However, treatment with melatonin simultane- ously prevented to a significant extent the alterations in carbo- hydrate and lipid metabolism and oxidative stress. Conclusions: Melatonin is a potent deprogrammer of neonatal corticosterone programming effects and the adult thrifty phenotype alteration to a diabetogenic challenge. Keywords: Corticosterone, diabetes, melatonin, neonatal, stress Introduction Recent epidemiological studies increasingly relate the incidence of many adult onset disorders like diabetes, obesity, hyperten- sion and other cardiovascular diseases to many early life experi- ences to which a fetus may be exposed to [1–5]. Most metabolic disorders and cardiovascular complications in the adults due to in utero restrictions come under the category of “Trify pheno- type”, a condition hypothesized as programming efect of imme- diate adaptation to the foetal experience for a thrify postnatal life style [6]. Apparently, programming occurs during critical windows of development and predisposes such individuals to adult pathophysiology as a long-term consequence. Some of the recent studies using several animal models of programming have highlighted the role of imprinted experiences in the foetal period in modulating physiological and metabolic alterations as long lasting adult feature [7–10]. Compared to foetal programming, neonatal programming has received scant attention, despite being also a critical window of development. Hormonal disturbances/perturbations in the neonatal period are likely to have enduring efects in program- ming, as hormones represent the link between the genome and the environment and can produce a range of phenotypes from the same genome by plasticity changes. Except for our studies on neonatal programming by melatonin, corticosterone and thyroxine on adult male gonadal functions and neuroendocrine reproduc- tive, adrenal and thyroid axes [11–13], there are no studies on the efects of neonatal programming by hormones. Postnatal glucocorticoid exposure induced alterations in adult phenotype have received some attention in recent times due to the practice of postnatal glucocorticoid therapy to combat respiratory distress syndrome in infants [14,15]. We previously reported on neonatal corticosterone programming induced adult plasticity alterations in metabolic features and tissue oxidative stress [16]. Te present study extends the above fndings further by assessing the impact of experimentally induced diabetes in animals programmed for a thrify phenotype by neonatal corticosterone programming and the deprogramming efcacy of melatonin. Materials and methods Experimental animals Albino Wistar rats of both sexes weighing 200–250 g used for the study were maintained under 12:12 light and dark schedule and 21–23°C temperature regimen and provided with standard rat chow and water ad libitum throughout the experimental period. When the mated females delivered pups, equal number of pups of both sexes was assigned to lactating mothers. Pups received corticosterone and/or melatonin from day 2 post partum until postnatal day (PND) 14. Control and treated rats were weaned on PND 21 and housed in separate cages depending on their treatment and sex and were maintained on standard rat chow and water ad libitum until 120 days. At the age of 120 days, diabetes was induced in both control and programmed rats and, rats with serum glucose above 300 mg/dl were considered for further experimentation. Neonatal corticosterone programs for thrifty phenotype adult diabetic manifestations and oxidative stress: countering effect of melatonin as a deprogrammer Darshee B. Baxi, Prem Kumar Singh, Kauresh D. Vachhrajani & Ramachandran A. V. Department of Zoology, Faculty of Science, Division of Metabolic Endocrinology, The M.S. University of Baroda, Gujarat, India Correspondence: Dr. Darshee Baxi, Department of Zoology, Faculty of Science, Division of Metabolic Endocrinology, Te M.S. University of Baroda, Vadodara 390002, Gujarat, India. Tel: +91 0265 2388013. E-mail: darsheebaxi@hotmail.com, mailtoavrcn@yahoo.co.in J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by HINARI on 10/14/12 For personal use only.