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Dive into the research topics where Alexandra I. Zugno is active.

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Featured researches published by Alexandra I. Zugno.


Neurochemical Research | 2009

Mitochondrial Dysfunction and Psychiatric Disorders

Gislaine T. Rezin; Graziela Amboni; Alexandra I. Zugno; João Quevedo; Emilio L. Streck

Mitochondrial oxidative phosphorylation is the major ATP-producing pathway, which supplies more than 95% of the total energy requirement in the cells. Damage to the mitochondrial electron transport chain has been suggested to be an important factor in the pathogenesis of a range of psychiatric disorders. Tissues with high energy demands, such as the brain, contain a large number of mitochondria, being therefore more susceptible to reduction of the aerobic metabolism. Mitochondrial dysfunction results from alterations in biochemical cascade and the damage to the mitochondrial electron transport chain has been suggested to be an important factor in the pathogenesis of a range of neuropsychiatric disorders, such as bipolar disorder, depression and schizophrenia. Bipolar disorder is a prevalent psychiatric disorder characterized by alternating episodes of mania and depression. Recent studies have demonstrated that important enzymes involved in brain energy are altered in bipolar disorder patients and after amphetamine administration, an animal model of mania. Depressive disorders, including major depression, are serious and disabling. However, the exact pathophysiology of depression is not clearly understood. Several works have demonstrated that metabolism is impaired in some animal models of depression, induced by chronic stress, especially the activities of the complexes of mitochondrial respiratory chain. Schizophrenia is a devastating mental disorder characterized by disturbed thoughts and perception, alongside cognitive and emotional decline associated with a severe reduction in occupational and social functioning, and in coping abilities. Alterations of mitochondrial oxidative phosphorylation in schizophrenia have been reported in several brain regions and also in platelets. Abnormal mitochondrial morphology, size and density have all been reported in the brains of schizophrenic individuals. Considering that several studies link energy impairment to neuronal death, neurodegeneration and disease, this review article discusses energy impairment as a mechanism underlying the pathophysiology of some psychiatric disorders, like bipolar disorder, depression and schizophrenia.


Neuroreport | 2000

Methylmalonate administration decreases Na+,K+-ATPase activity in cerebral cortex of rats.

Angela Terezinha de Souza Wyse; Emilio L. Streck; Sonja Verginia Tamborena Barros; Ana Maria Brusque; Alexandra I. Zugno; Moacir Wajner

Buffered methylmalonate (MMA) was injected s.c. into rats twice a day at 8 h intervals from 5 to 25 days of age (chronic treatment), or into 10-day-old rats three times a day at 1 h intervals (acute treatment). Control rats received saline in the same volumes. Na+, K+-ATPase and Mg2+-ATPase activities were determined in the synaptic plasma membranes from cerebral cortex of rats. Na+, K+-ATPase activity was reduced by 30–40% in MMA-treated rats, whereas Mg2+-ATPase activity was not. In contrast, MMA at final concentrations ranging from 0.1 to 2.0 mM had no in vitro effect on these enzyme activities. However, when brain homogenates were incubated with 2 mM MMA before membrane preparation, Na+, K+-ATPase activity was decreased by 44%. Furthermore, this reduction was totally prevented by the simultaneous addition of glutathione and MMA, suggesting that oxidation of thiol groups or other oxidative damage to the enzyme could be responsible for this effect.


Aging and Disease | 2015

The involvement of BDNF, NGF and GDNF in aging and Alzheimer’s disease

Josiane Budni; Tatiani Bellettini-Santos; Francielle Mina; Michelle Lima Garcez; Alexandra I. Zugno

Aging is a normal physiological process accompanied by cognitive decline. This aging process has been the primary risk factor for development of aging-related diseases such as Alzheimers disease (AD). Cognitive deficit is related to alterations of neurotrophic factors level such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and glial cell-derived neurotrophic factor (GDNF). These strong relationship between aging and AD is important to investigate the time which they overlap, as well as, the pathophysiological mechanism in each event. Considering that aging and AD are related to cognitive impairment, here we discuss the involving these neurotrophic factors in the aging process and AD.


Metabolic Brain Disease | 2002

Pretreatment with vitamins E and C prevent the impairment of memory caused by homocysteine administration in rats

Eleonora Araújo dos Reis; Alexandra I. Zugno; Renata Franzon; Bárbara Tagliari; Cristiane Matté; Marcelo Lazzaron Lammers; Carlos Alexandre Netto; Angela Terezinha de Souza Wyse

Homocystinuria is a metabolic disorder caused by deficiency of cystathione β-synthase activity leading to tissue accumulation of homocysteine (Hcy); affected patients present neurological dysfunction. Considering that Hcy induces free radical formation and that memory is impaired by oxidative stress, in the present study we investigated the effect of an acute administration of Hcy on retrieval of step-down inhibitory avoidance in adult rats. The action of vitamins E and C on the effects produced by Hcy was also tested. Adult Wistar rats were pretreated for 1 week with daily i.p. administration of saline (control group) and vitamins E and C (vitamin E 40 mg/kg and vitamin C 100 mg/kg). Hcy (11 mmol/kg) or an equivalent volume of 0.9% saline were administered 1 h before training, 1 h before testing, or immediately after training sessions. Memory was significantly impaired in Hcy-treated group, whereas the rats chronically treated with vitamins E and C had this effect prevented. Present data strongly indicate that Hcy administration impairs memory, an effect probably mediated by oxidative stress since treatment with vitamins E and C prevented amnesia. Assuming the possibility that this might occur in the human condition, reported results may be relevant to explain, at least in part, neurologic dysfunction associated with homocystinuria.


Progress in Neuro-psychopharmacology & Biological Psychiatry | 2009

Different sub-anesthetic doses of ketamine increase oxidative stress in the brain of rats

Larissa de Oliveira; Cecília Marly dos S. Spiazzi; Thaize Bortolin; Leila Canever; Fabricia Petronilho; Franciele Mina; Felipe Dal-Pizzol; João Quevedo; Alexandra I. Zugno

Schizophrenia is a complex neuropsychiatric disorder in which symptoms can be classified as either positive, such as delusions and hallucinations, or negative, such as blunted affect and social withdrawal. However, the mechanisms underlying this disease are poorly understood. There is evidence that reactive oxygen species (ROS) play an important role in the pathogenesis of many diseases, particularly those which are neurological and psychiatric in nature. Ketamine has been used to induce a schizophrenia-like condition as an animal model in which to study this condition. In the present study we tested the effects of sub-anesthetic doses of ketamine on various parameters of oxidative stress in the brain of rats. Our results indicate that lipid peroxidation and tissue protein oxidation were affected by varying sub-anesthetic doses of ketamine in multiple cerebral structures. Additionally, the activity of the antioxidant enzymes CAT and SOD was measured and was also found to be altered in most of the structures tested. In conclusion, we observe an increase in oxidative damage marked by an increase in lipid peroxidation, oxidative protein damage and a decrease in enzymatic defenses, in an animal model of schizophrenia. Given that oxidative stress could be related to schizophrenia, these findings may explain, at least in part, the mechanisms underlying in this disease.


Schizophrenia Research | 2012

Effects of omega-3 dietary supplement in prevention of positive, negative and cognitive symptoms: A study in adolescent rats with ketamine-induced model of schizophrenia

Clarissa Severino Gama; Lara Canever; Bruna Schilling Panizzutti; Carolina Gubert; Laura Stertz; Raffael Massuda; Mariana Pedrini; Renata D. De Luca; Daiane B. Fraga; Alexandra S. Heylmann; Pedro F. Deroza; Alexandra I. Zugno

Omega-3 has shown efficacy to prevent schizophrenia conversion in ultra-high risk population. We evaluated the efficacy of omega-3 in preventing ketamine-induced effects in an animal model of schizophrenia and its effect on brain-derived neurotrophic factor (BDNF). Omega-3 or vehicle was administered in Wistar male rats, both groups at the 30th day of life for 15days. Each group was split in two to receive along the following 7days ketamine or saline. Locomotor and exploratory activities, memory test and social interaction between pairs were evaluated at the 52nd day of life. Prefrontal-cortex, hippocampus and striatum tissues were extracted right after behavioral tasks for mRNA BDNF expression analysis. Bloods for serum BDNF were withdrawn 24h after the end of behavioral tasks. Locomotive was increased in ketamine-treated group compared to control, omega-3 and ketamine plus omega-3 groups. Ketamine group had fewer contacts and interaction compared to other groups. Working memory and short and long-term memories were significantly impaired in ketamine group compared to others. Serum BDNF levels were significantly higher in ketamine plus omega-3 group. There was no difference between groups in prefrontal-cortex, hippocampus and striatum for mRNA BDNF expression. Administration of omega-3 in adolescent rats prevents positive, negative and cognitive symptoms in a ketamine animal model of schizophrenia. Whether these findings are consequence of BDNF increase it is unclear. However, this study gives compelling evidence for larger clinical trials to confirm the use of omega-3 to prevent schizophrenia and for studies to reinforce the beneficial role of omega-3 in brain protection.


Neuroscience | 2014

Omega-3 prevents behavior response and brain oxidative damage in the ketamine model of schizophrenia.

Alexandra I. Zugno; H.L. Chipindo; Ana Maria Volpato; Josiane Budni; Amanda V. Steckert; M.B. de Oliveira; Alexandra S. Heylmann; F. da Rosa Silveira; Gustavo Antunes Mastella; S.G. Maravai; Patrícia Gomes Wessler; A.R. Binatti; B. Panizzutti; Patrícia Fernanda Schuck; João Quevedo; Clarissa Severino Gama

Supplementation with omega-3 has been identified as an adjunctive alternative for the treatment of psychiatric disorders, in order to minimize symptoms. Considering the lack of understanding concerning the pathophysiology of schizophrenia, the present study hypothesized that omega 3 prevents the onset of symptoms similar to schizophrenia in young Wistar rats submitted to ketamine treatment. Moreover, the role of oxidative stress in this model was assessed. Omega-3 (0.8g/kg) or vehicle was given by orogastric gavage once daily. Both treatments were performed during 21days, starting at the 30th day of life in young rats. After 14days of treatment with omega-3 or vehicle, a concomitant treatment with saline or ketamine (25mg/kg ip daily) was started and maintained until the last day of the experiment. We evaluated the pre-pulse inhibition of the startle reflex, activity of antioxidant systems and damage to proteins and lipids. Our results demonstrate that supplementation of omega-3 prevented: decreased inhibition of startle reflex, damage to lipids in the hippocampus and striatum and damage to proteins in the prefrontal cortex. Furthermore, these changes are associated with decreased GPx in brain tissues evaluated. Together, our results suggest the prophylactic role of omega-3 against the outcome of symptoms associated with schizophrenia.


Neurochemical Research | 2010

Oxidative Mechanisms of Brain Dysfunction During Sepsis

Felipe Dal-Pizzol; Cristiane Ritter; Omar J. Cassol-Jr; Gislaine T. Rezin; Fabricia Petronilho; Alexandra I. Zugno; João Quevedo; Emilio L. Streck

Oxidative stress has drawn a lot of attention in the past few decades, since it has been reported to participate in the mechanism of many diseases. Therefore, it seemed to be a good rationale to aim oxidative stress on therapeutic research. Sepsis is a complex systemic syndrome characterized by an imbalance between pro- and anti-inflammatory responses to a pathogen; its pathophysiology is a dynamic process which involves components of the immune system, the coagulation pathway, parenchymal cells, and the endocrine and metabolic pathways. It is well characterized that oxidative stress plays a crucial role in sepsis development, but the relation between central nervous system dysfunction and oxidative stress during sepsis is not well understood. Thus, we here summarize the current knowledge on the role of free radicals in the development of brain dysfunction in sepsis focusing on oxidative damage and the redox control of brain inflammatory pathways.


Behavioural Pharmacology | 2011

Behavioral and neurochemical effects of sodium butyrate in an animal model of mania.

Morgana Moretti; Samira S. Valvassori; Roger B. Varela; Camila L. Ferreira; Natália Rochi; Joana Benedet; Giselli Scaini; Flávio Kapczinski; Emilio L. Streck; Alexandra I. Zugno; João Quevedo

The present study investigated the effect of the histone deacetylase inhibitor, sodium butyrate (SB), on locomotor behavior and on mitochondrial respiratory-chain complexes activity in the brain of rats subjected to an animal model of mania induced by d-amphetamine (d-AMPH). In the reversal treatment, Wistar rats were first treated with d-AMPH or saline (Sal) for 14 days. Thereafter, between days 8 and 14, rats were administered SB or Sal. In the prevention treatment, rats were treated with SB or Sal for 14 days and received d-AMPH or Sal between days 8 and 14. The d-AMPH treatment increased locomotor behavior in Sal-treated rats under reversion and prevention treatment, and SB reversed and prevented d-AMPH-related hyperactivity. Moreover, d-AMPH decreased the activity of mitochondrial respiratory-chain complexes in Sal-treated rats in the prefrontal cortex, hippocampus, striatum, and amygdala in both experiments, and SB was able to reverse and prevent this impairment. The present study suggests that the mechanism of action of SB involves induction of mitochondrial function in parallel with behavioral changes, reinforcing the need for more studies on histone deacetylase inhibitors as a possible target for new medications for bipolar disorder treatment.


Journal of Psychiatric Research | 2012

Evaluation of behavioral and neurochemical changes induced by ketamine in rats: Implications as an animal model of mania

Fernando V. Ghedim; Daiane B. Fraga; Pedro F. Deroza; Mariana B. Oliveira; Samira S. Valvassori; Amanda V. Steckert; Josiane Budni; Felipe Dal-Pizzol; João Quevedo; Alexandra I. Zugno

Bipolar disorder (BD) is a chronic, prevalent, and highly debilitating psychiatric illness characterized by recurrent manic and depressive episodes. Mood stabilizing agents such as lithium and valproate are two primary drugs used to treat BD. To develop a novel animal model of mania (hallmark of BD), it is important to assess the therapeutic and prophylactic effect of these mood stabilizers on the new candidate target animal model. The present work investigates the therapeutic and prophylactic value of lithium and valproate in a novel preclinical animal model of mania, induced by ketamine. In the prevention protocol, wistar rats were pretreated with lithium (47.5 mg/kg, i.p., twice a day), valproate (200 mg/kg, i.p., twice a day), or saline (i.p., twice a day) for 14 days. Between days 8 and 14, the rats were treated with ketamine (25 mg/kg, i.p.) or saline. In the reversal protocol, rats first received ketamine (25 mg/kg, i.p.) or saline. After, the administration of lithium, valproate, or saline was carried out for seven days. Our results indicated that lithium and valproate reversed and prevented ketamine-induced hyperlocomotion. Moreover, lithium and valproate reversed (prefrontal cortex, hippocampus, and striatum) and prevented (prefrontal cortex, hippocampus, striatum, and amygdala) the increase of the TBARS level induced by ketamine. The protein carbonyl formation, induced by ketamine, was reversed by lithium and valproate in the prefrontal cortex, hippocampus, and striatum, and prevented only in the amygdala. These findings support the notion that the administration of ketamine might be a promising pharmacological animal model of mania, which could play a role in the pathophysiology of BD.

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Emilio L. Streck

Universidade do Extremo Sul Catarinense

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Giselli Scaini

University of Texas Health Science Center at Houston

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Daiane B. Fraga

Universidade do Extremo Sul Catarinense

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Josiane Budni

Universidade do Extremo Sul Catarinense

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Pedro F. Deroza

Universidade do Extremo Sul Catarinense

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Renata D. De Luca

Universidade do Extremo Sul Catarinense

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Samira S. Valvassori

Universidade do Extremo Sul Catarinense

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Alexandra S. Heylmann

Universidade do Extremo Sul Catarinense

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Fernando V. Ghedim

Universidade do Extremo Sul Catarinense

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