Rapid eye movement sleep deprivation induces changes in the high-affinity binding of [H-3]-ouabain to the rat cortical membranes

Rapid eye movement sleep (REMS) suppresses seizures. On the other hand, REMS deprivation (REMSD) increases brain susceptibility to seizures. Sodium-postassium/ATPase is involved in the control of brain excitability. Ouabain, a cardiotonic glycoside, binds to a regulatory extracellular allosteric site in the sodium-potassium/ATPase inhibiting/stimulating its activity depending on its concentration. Endogenous ouabain-like substances exist in the brain; therefore, changes in the ouabain binding site may be involved in the increased brain excitability induced by REMSD. Adult, Wistar male rats were deprived of REMS for 96 hours by the flower-pot method (REMSD). A stress control group was kept in the same environment on a larger platform (LP). A third group of rats was kept in the same room in their home-cages (CONTROL). After REMSD all rats were sacrificed by decapitation and their cerebral cortex dissected. High-affinity [H-3]-ouabain binding was carried out in cortical crude membrane preparation using 8 concentrations of [H-3]-ouabain (1-24 nM). the results show a statistically significant increase of KID in the REMSD rats compared to both CONTROL and LP groups. There were no statistically significant differences in th B-max among the experimental groups. There was also no change either in cortical activity of K+ stimulated p-nitrophenylphosphatase, the dephosphorylation reaction of phosphorylated sodium-potassium/ATPase or in Mg2+-stimulated p-nitrophenylphosphatase. An increase in the KD of [H-3]-ouabain binding to the sodium-potassium/ATPase in REMSD rats indicates a lower affinity to the endogenous inhibitors/stimulators of the enzyme. Therefore, this decreased affinity of the endogenous ouabain-like substances may be involved in the increased excitability induced by REMSD. (c) 2005 Elsevier Ireland Ltd. All rights reserved.Universidade Federal de São Paulo, Escola Paulista Med, Dept Psicobiol, BR-04023 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Psicobiol, BR-04023 São Paulo, BrazilWeb of Scienc

Behavioral differences between subgroups of rats with high and low threshold to clonic convulsions induced by DMCM, a benzodiazepine inverse agonist

In epileptic patients, there is a high incidence of psychiatric comorbidities, such as anxiety. Gamma-aminobutyric acid (GABA) ionotropic receptor GABA(A)/benzodiazepine allosteric site is involved in both epilepsy and anxiety. This involvement is based on the fact that benzodiazepine allosteric site agonists are anticonvulsant and anxiolytic drugs; on the other hand, benzodiazepine inverse agonists are potent convulsant and anxiogenic drugs. the aim of this work was to determine if subgroups of rats selected according to their susceptibility to clonic convulsions induced by a convulsant dose 50% (CD50) of DMCM, a benzodiazepine inverse agonist, would differ in behavioral tests commonly used to measure anxiety (elevated plus-maze, open field) and depression (forced swimming test). in the first experiment, subgroups of adult male Wistar rats were selected after a single dose of DMCM and in the second experiment they were selected after two injections of DMCM given after an interval of 1 week. Those rats presenting full clonic convulsions were termed Low Threshold rats to DMCM-induced clonic convulsions (LTR) and those not having clonic convulsions High Threshold rats to DMCM-induced clonic convulsions (HTR). in both experiments, only those rats presenting full clonic convulsions induced by DMCM and those not showing any signs of motor disturbances were used in the behavioral tests. the results showed that the LTR subgroup selected after two injections of a CD50 of DMCM spent a significantly lower time in the open arms of the elevated plus-maze and in the off the walls area of the open field; moreover, this group also presented a higher number of rearings in the open field. There were no significant differences between HTR and LTR subgroups in the forced swimming test. LTR and HTR subgroups selected after only one injection of DMCM did not differ in the three behavioral tests. To verify if the behavioral differences between HTR and LTR subgroups of rats selected after two injections of DMCM were due to the clonic convulsion, another experiment was carried out in which subgroups of rats susceptible and nonsusceptible to clonic convulsions induced by a CD50 of picrotoxin, a GABA(A) receptor channel blocker, were selected and submitted to the elevated plus-maze and open field tests. the results obtained did not show any significant differences between these two subgroups in the elevated plus-maze and open field tests. in another approach to determine the relation between fear/anxiety and susceptibility to clonic convulsions, subgroups of rats were selected in the elevated plus-maze as more or less fearful/anxious. the CD50 for clonic convulsions induced by DMCM was determined for each of these two subgroups. the results showed a significantly lower CD50 for the more fearful/anxious subgroup, which means a higher susceptibility to clonic convulsions induced by DMCM. the present findings show a relation between susceptibility to clonic convulsions and fear/anxiety and vice versa which may be due to differences in the assembly of GABA(A)/allosteric benzodiazepine site receptors in regions of the brain. (c) 2005 Elsevier Inc. All rights reserved.Universidade Federal de São Paulo, Dept Psicobiol, Escola Paulista Med, BR-0402390 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, Escola Paulista Med, BR-0402390 São Paulo, BrazilWeb of Scienc

Effects of glucosyl-hesperidin and physical training on body weight, plasma lipids, oxidative status and vascular reactivity of rats fed with high-fat diet

Tiago Tomazini Gonçalves,1 Carolina M Lazaro,1 Fernanda G De Mateo,1 Marcela CB Campos,1 Jackeline GB Mezencio,1 Mario A Claudino,1 Patrícia de O Carvalho,1 R Clinton Webb,2 Fernanda BM Priviero1,2 1Laboratory of Multidisciplinary Research, Universidade São Francisco, Bragança Paulista, São Paulo, Brazil; 2Department of Physiology, Medical College of Georgia, Augusta University, Augusta, GA, USA Objective: The aim of the study was to evaluate the effects of supplementation with glucosyl hesperidin (GH), with or without physical training, on body weight, fat depot, glucose and plasma lipids, oxidative status and vascular function of rats fed with high-fat diet (HFD). Methods: After weaning, male Wistar rats were fed with an HFD plus fructose for 12 weeks and started receiving oral antioxidant supplementation and/or physical training after the fourth week of diet for eight further weeks. Body weight, epididymal and retroperitoneal fat, plasma glucose and lipids, oxidative status and mesenteric artery reactivity were evaluated. Results: Rats fed with HFD presented higher body weight gain and fat accumulation compared to control rats, while GH supplementation did not influence these parameters. Physical training reduced the body weight gain and fat accumulation and modulated the oxidative status by increasing superoxide dismutase activity and total antioxidant capacity and reducing lipid peroxidation. GH alone decreased lipid peroxidation. However, when given to exercised rats, it impaired the response elicited by physical training. HFD caused endothelial dysfunction, and neither GH nor physical exercise prevented it. Potency of sodium nitroprusside was increased in exercised animals but not in GH-supplemented rats. Conclusion: Physical exercise partially decreased the body fat accumulation, decreased plasma levels of glucose and lipids and improved general oxidative status and endothelium-independent relaxation in mesenteric arteries of rats fed with HFD. GH exhibited benefits only in the oxidative status. However, GH given in association with physical exercise did not cause further changes in addition to those promoted by physical exercise. On the contrary, in exercised animals, GH prevented those changes elicited by physical training in plasma glucose and lipids, oxidative status and endothelium-independent relaxation. Keywords: high-fat diet, physical activity, oxidative stress, antioxidants, obesity, physical exercise, supplementation, flavonoids, reactive oxygen specie