Rosana Alves - Academia.edu (original) (raw)

Papers by Rosana Alves

Research paper thumbnail of High- and Low-Rearing Rats Differ in the Brain Excitability Controlled by the Allosteric Benzodiazepine Site in the GABA<sub>A</sub> Receptor

Journal of Behavioral and Brain Science, 2012

Rearing is an exploratory behavior induced by novelty, such as exposure to an open field. Stimula... more Rearing is an exploratory behavior induced by novelty, such as exposure to an open field. Stimulation of certain brain regions, including the hippocampus, induces both rearing and clonic convulsions. Brain excitability is controlled by gamma-aminobutyric acid (GABA) inhibitory neurotransmission through its ionotropic GABA A /allosteric benzodiazepine site. Drugs that decrease GABA A receptor fast inhibitory neurotransmission induce clonic convulsions and rearing when injected into the hippocampus. Therefore, individual differences in rearing behavior may be related to the susceptibility to clonic convulsions, which could involve differences in brain excitability controlled by GABA A /allosteric benzodiazepine site receptors. Adult, male Wistar rats were divided into high-(HR) and low-rearing (LR) groups based on the number of rearings in the open field test. Groups of HR and LR rats were challenged with convulsant drugs that antagonize GABA neurotransmission via different mechanisms of action (3-mercaptopropionic acid, a glutamate decarboxilase inhibitor; bicuculline, a GABA A receptor antagonist; pentylenetetrazol and picrotoxin, both GABA A receptor chloride channel blockers and DMCM, a benzodiazepine inverse agonist). The convulsant doses that induced 50% of clonic convulsions were determined for each drug. The LR rats had a higher susceptibility (a lower convulsant dose 50%) to clonic convulsions induced by DMCM than the HR rats, but there were no differences between the groups in the susceptibility to tonic convulsions induced by the same drug. There were no significant differences in the convulsant dose 50% for clonic convulsions between the groups for all other drugs injected. In another experiment, additional HR and LR rats were injected with a sedative-hypnotic dose of diazepam, which caused a significantly higher hypnotic effect (sleeping-time) in the LR rats than in the HR rats. The LR group was also shown to have a significantly lower density of [ 3 H]-Flunitrazepam bound to the GABA A receptor in hippocampal membranes. Our data suggest that inter-individual differences in rearing are related, at least in part, to the GABA inhibitory neurotransmission controlled by the benzodiazepine allosteric site in the GABA A receptor.

Research paper thumbnail of Ischemia/reperfusion-induced alterations of enzymatic and signaling functions of the rat cardiac Na+/K+-ATPase: protection by ouabain preconditioning

Physiological Reports, 2016

Cardiac glycosides (CG) are traditionally known as positive cardiac inotropes that inhibit Na + /... more Cardiac glycosides (CG) are traditionally known as positive cardiac inotropes that inhibit Na + /K +-ATPase-dependent ion transport. CG also trigger-specific signaling pathways through the cardiac Na + /K +-ATPase, with beneficial effects in ischemia/reperfusion (I/R) injury (e.g., ouabain preconditioning, known as OPC) and hypertrophy. Our current understanding of hypersensitivity to CG and subsequent toxicity in the ischemic heart is mostly based on specific I/Rinduced alterations of the Na + /K +-ATPase enzymatic function and has remained incomplete. The primary goal of this study was to investigate and compare the impact of I/R on Na + /K +-ATPase enzymatic and signaling functions. Second, we assessed the impact of OPC on both functions. Langendorff-perfused rat hearts were exposed to 30 min of ischemia and 30 min of reperfusion. At the inotropic concentration of 50 lmol/L, ouabain increased ERK and Akt phosphorylation in control hearts. In I/R hearts, this concentration did not induced positive inotropy and failed to induce Akt or ERK phosphorylation. The inotropic response to dobutamine as well as insulin signaling persisted, suggesting specific alterations of Na + /K +-ATPase. Indeed, Na + /K +-ATPase protein expression was intact, but the enzyme activity was decreased by 60% and the enzymatic function of the isoform with high affinity for ouabain was abolished following I/R. Strikingly, OPC prevented all I/R-induced alterations of the receptor. Further studies are needed to reveal the respective roles of I/R-induced modulations of Na + /K +-ATPase enzymatic and signaling functions in cardiomyocyte death.

Research paper thumbnail of Estudo comportamental farmacológico, bioquímico e hormonal em subgrupos de ratos selecionados pelo comportamento de empinar no teste do campo aberto

Research paper thumbnail of High and low rearing subgroups of rats selected in the open field differ in the activity of K+-stimulated p-nitrophenylphosphatase in the hippocampus

Brain Research, 2005

is of paramount importance for the proper functioning of the organism. The enzyme is involved in ... more is of paramount importance for the proper functioning of the organism. The enzyme is involved in several aspects of brain function, such as the repolarization of the neuronal membranes and neurotransmitters uptake/release. Therefore, individual differences in the activity of brain Na + /K +-ATPase may result in differences in the functioning of the brain, which, in consequence, could lead to behavioral divergences. Individual differences in rearing, an exploratory behavior, have been shown to be genetically determined. In rats, the inhibition of the activity of Na + /K +-ATPase was reported to induce changes in the exploratory behavior. The aim of this work was to verify if subgroups of rats selected according to the number of rearings (high and low rearing subgroups) in the open field test differ in the activity of Na + /K +-ATPase in brain regions. Adult, male outbred Wistar rats were selected in the open field test according to the number of rearings in subgroups of high (HR) and low (LR) rearing responders. After a rest of about 20 days after the open field session, HR and LR rats were sacrificed. In the first experiment, frontal cortex, striatum, brainstem, hippocampus and the amygdala (including the overlying limbic cortex) were dissected. The reaction of dephosphorylation of Na + /K +-ATPase (K + stimulated pnitrophenylphosphatase) was assayed in homogenates rich in synaptosomes. The results obtained showed a statistically significant higher activity of K + p-nitrophenylphosphatase only in the hippocampus of HR subgroup of rats. This result was replicated in two other subsequent experiments with different HR and LR subgroups of rats selected at different times of the year. Our data suggest that the difference in the activity of Na + /K +-ATPase in the hippocampus is innate and is involved in the expression of the rearing behavior.

Research paper thumbnail of Effects of intermittent fasting on age-related changes on Na,K-ATPase activity and oxidative status induced by lipopolysaccharide in rat hippocampus

Neurobiology of aging, Jan 28, 2015

Chronic neuroinflammation is a common characteristic of neurodegenerative diseases, and lipopolys... more Chronic neuroinflammation is a common characteristic of neurodegenerative diseases, and lipopolysaccharide (LPS) signaling is linked to glutamate-nitric oxide-Na,K-ATPase isoforms pathway in central nervous system (CNS) and also causes neuroinflammation. Intermittent fasting (IF) induces adaptive responses in the brain that can suppress inflammation, but the age-related effect of IF on LPS modulatory influence on nitric oxide-Na,K-ATPase isoforms is unknown. This work compared the effects of LPS on the activity of α1,α2,3 Na,K-ATPase, nitric oxide synthase gene expression and/or activity, cyclic guanosine monophosphate, 3-nitrotyrosine-containing proteins, and levels of thiobarbituric acid-reactive substances in CNS of young and older rats submitted to the IF protocol for 30 days. LPS induced an age-related effect in neuronal nitric oxide synthase activity, cyclic guanosine monophosphate, and levels of thiobarbituric acid-reactive substances in rat hippocampus that was linked to cha...

Research paper thumbnail of High- and Low-Rearing Rats Differ in the Brain Excitability Controlled by the Allosteric Benzodiazepine Site in the GABA<sub>A</sub> Receptor

Journal of Behavioral and Brain Science, 2012

Rearing is an exploratory behavior induced by novelty, such as exposure to an open field. Stimula... more Rearing is an exploratory behavior induced by novelty, such as exposure to an open field. Stimulation of certain brain regions, including the hippocampus, induces both rearing and clonic convulsions. Brain excitability is controlled by gamma-aminobutyric acid (GABA) inhibitory neurotransmission through its ionotropic GABA A /allosteric benzodiazepine site. Drugs that decrease GABA A receptor fast inhibitory neurotransmission induce clonic convulsions and rearing when injected into the hippocampus. Therefore, individual differences in rearing behavior may be related to the susceptibility to clonic convulsions, which could involve differences in brain excitability controlled by GABA A /allosteric benzodiazepine site receptors. Adult, male Wistar rats were divided into high-(HR) and low-rearing (LR) groups based on the number of rearings in the open field test. Groups of HR and LR rats were challenged with convulsant drugs that antagonize GABA neurotransmission via different mechanisms of action (3-mercaptopropionic acid, a glutamate decarboxilase inhibitor; bicuculline, a GABA A receptor antagonist; pentylenetetrazol and picrotoxin, both GABA A receptor chloride channel blockers and DMCM, a benzodiazepine inverse agonist). The convulsant doses that induced 50% of clonic convulsions were determined for each drug. The LR rats had a higher susceptibility (a lower convulsant dose 50%) to clonic convulsions induced by DMCM than the HR rats, but there were no differences between the groups in the susceptibility to tonic convulsions induced by the same drug. There were no significant differences in the convulsant dose 50% for clonic convulsions between the groups for all other drugs injected. In another experiment, additional HR and LR rats were injected with a sedative-hypnotic dose of diazepam, which caused a significantly higher hypnotic effect (sleeping-time) in the LR rats than in the HR rats. The LR group was also shown to have a significantly lower density of [ 3 H]-Flunitrazepam bound to the GABA A receptor in hippocampal membranes. Our data suggest that inter-individual differences in rearing are related, at least in part, to the GABA inhibitory neurotransmission controlled by the benzodiazepine allosteric site in the GABA A receptor.

Research paper thumbnail of Ischemia/reperfusion-induced alterations of enzymatic and signaling functions of the rat cardiac Na+/K+-ATPase: protection by ouabain preconditioning

Physiological Reports, 2016

Cardiac glycosides (CG) are traditionally known as positive cardiac inotropes that inhibit Na + /... more Cardiac glycosides (CG) are traditionally known as positive cardiac inotropes that inhibit Na + /K +-ATPase-dependent ion transport. CG also trigger-specific signaling pathways through the cardiac Na + /K +-ATPase, with beneficial effects in ischemia/reperfusion (I/R) injury (e.g., ouabain preconditioning, known as OPC) and hypertrophy. Our current understanding of hypersensitivity to CG and subsequent toxicity in the ischemic heart is mostly based on specific I/Rinduced alterations of the Na + /K +-ATPase enzymatic function and has remained incomplete. The primary goal of this study was to investigate and compare the impact of I/R on Na + /K +-ATPase enzymatic and signaling functions. Second, we assessed the impact of OPC on both functions. Langendorff-perfused rat hearts were exposed to 30 min of ischemia and 30 min of reperfusion. At the inotropic concentration of 50 lmol/L, ouabain increased ERK and Akt phosphorylation in control hearts. In I/R hearts, this concentration did not induced positive inotropy and failed to induce Akt or ERK phosphorylation. The inotropic response to dobutamine as well as insulin signaling persisted, suggesting specific alterations of Na + /K +-ATPase. Indeed, Na + /K +-ATPase protein expression was intact, but the enzyme activity was decreased by 60% and the enzymatic function of the isoform with high affinity for ouabain was abolished following I/R. Strikingly, OPC prevented all I/R-induced alterations of the receptor. Further studies are needed to reveal the respective roles of I/R-induced modulations of Na + /K +-ATPase enzymatic and signaling functions in cardiomyocyte death.

Research paper thumbnail of Estudo comportamental farmacológico, bioquímico e hormonal em subgrupos de ratos selecionados pelo comportamento de empinar no teste do campo aberto

Research paper thumbnail of High and low rearing subgroups of rats selected in the open field differ in the activity of K+-stimulated p-nitrophenylphosphatase in the hippocampus

Brain Research, 2005

is of paramount importance for the proper functioning of the organism. The enzyme is involved in ... more is of paramount importance for the proper functioning of the organism. The enzyme is involved in several aspects of brain function, such as the repolarization of the neuronal membranes and neurotransmitters uptake/release. Therefore, individual differences in the activity of brain Na + /K +-ATPase may result in differences in the functioning of the brain, which, in consequence, could lead to behavioral divergences. Individual differences in rearing, an exploratory behavior, have been shown to be genetically determined. In rats, the inhibition of the activity of Na + /K +-ATPase was reported to induce changes in the exploratory behavior. The aim of this work was to verify if subgroups of rats selected according to the number of rearings (high and low rearing subgroups) in the open field test differ in the activity of Na + /K +-ATPase in brain regions. Adult, male outbred Wistar rats were selected in the open field test according to the number of rearings in subgroups of high (HR) and low (LR) rearing responders. After a rest of about 20 days after the open field session, HR and LR rats were sacrificed. In the first experiment, frontal cortex, striatum, brainstem, hippocampus and the amygdala (including the overlying limbic cortex) were dissected. The reaction of dephosphorylation of Na + /K +-ATPase (K + stimulated pnitrophenylphosphatase) was assayed in homogenates rich in synaptosomes. The results obtained showed a statistically significant higher activity of K + p-nitrophenylphosphatase only in the hippocampus of HR subgroup of rats. This result was replicated in two other subsequent experiments with different HR and LR subgroups of rats selected at different times of the year. Our data suggest that the difference in the activity of Na + /K +-ATPase in the hippocampus is innate and is involved in the expression of the rearing behavior.

Research paper thumbnail of Effects of intermittent fasting on age-related changes on Na,K-ATPase activity and oxidative status induced by lipopolysaccharide in rat hippocampus

Neurobiology of aging, Jan 28, 2015

Chronic neuroinflammation is a common characteristic of neurodegenerative diseases, and lipopolys... more Chronic neuroinflammation is a common characteristic of neurodegenerative diseases, and lipopolysaccharide (LPS) signaling is linked to glutamate-nitric oxide-Na,K-ATPase isoforms pathway in central nervous system (CNS) and also causes neuroinflammation. Intermittent fasting (IF) induces adaptive responses in the brain that can suppress inflammation, but the age-related effect of IF on LPS modulatory influence on nitric oxide-Na,K-ATPase isoforms is unknown. This work compared the effects of LPS on the activity of α1,α2,3 Na,K-ATPase, nitric oxide synthase gene expression and/or activity, cyclic guanosine monophosphate, 3-nitrotyrosine-containing proteins, and levels of thiobarbituric acid-reactive substances in CNS of young and older rats submitted to the IF protocol for 30 days. LPS induced an age-related effect in neuronal nitric oxide synthase activity, cyclic guanosine monophosphate, and levels of thiobarbituric acid-reactive substances in rat hippocampus that was linked to cha...