Molecular Neurobiology - Caspase-3 Mediates In Part Hippocampal Apoptosis in Sepsis
Clarissa Comim, Tatiana Barichello, Denis Grandgirard, Felipe Dal-Pizzol, João Quevedo e Stephen L. Leib
The brain is one of the first organs affected during sepsis development resulting in apoptosis for a short-term and cognitive impairment for a long-term. Despite its importance, the mechanisms of brain dysfunction during sepsis are not fully elucidated. Thus, we here, in an animal model of sepsis, evaluated apoptosis in the dentate gyrus cell layer of the hippocampus to document the involvement of caspase-3 in the pathogenesis of neuronal apoptosis. Wistar rats sham-operated or submitted to the cecal ligation and perforation (CLP) procedure were killed at 12, 24, 48 h, and 10 days after surgery for the determination of caspase-3 and apoptosis rate. In a separate cohort of animals, a caspase-3-specific inhibitor was administered and animals were killed at 12 h after sepsis. An increase in the number of apoptotic cells 12, 24, and 48 h by histopathological evaluations and an increase of caspase-3 apoptotic cells 12 and 24 h after sepsis induction were observed. The caspase-3 inhibitor decreases the number of apoptotic cells by histopathological evaluations but not by immunohistochemistry evaluations. Caspase-3 is involved in part in apoptosis in the dentate gyrus cell layer of the hippocampus in septic rats submitted by CLP.
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Pharmacology, Biochemistry, and Behavior - Tianeptine exerts neuroprotective effects in the brain tissue of rats exposed to the chronic stress model
Franciela Della, Helena Abelaira, Gislaine Réus, Altamir Antunes, Maria Augusta Santos, Giovanni Zappelinni, Amanda Steckert, Francieli Vuolo, Leticia S. Galant, Felipe Dal-Pizzol, Flávio Kapczinski e João Quevedo
Animal models of chronic stress represent valuable tools by which to investigate the behavioral, endocrine and neurobiological changes underlying stress-related psychopathologies, such as major depression, and the efficacy of antidepressant therapies. The present study was aimed at investigating the neurochemical effects of the antidepressant tianeptine in rats exposed to the chronic stress model. To this aim, rats were subjected to 40days of chronic unpredictable stressful stimuli, after which the animals received saline or tianeptine (15mg/kg) once a day for 7days. Additionally, IL-6, IL-1, TNF-α levels and oxidative stress parameters were assessed in the prefrontal cortex (PFC), hippocampus (HPC), amygdala (AMY) and nucleus accumbens (NAc) in all of the experimental groups studied. The results indicated that chronic mild stress and tianeptine did not exercise any effects on cytokines in all of the structures studied; in the PFC and AMY thiobarbituric acid reactive substances (TBARS) levels were decreased in control rats treated with tianeptine in the HPC; superoxide dismutase (SOD) activity was found to have decreased in stressed rats treated with saline in the PFC, HPC, AMY and NAc, and tianeptine reversed this effect; catalase (CAT) activity was found to have decreased in the PFC, HPC and NAc of stressed rats treated with saline, but was shown to have increased in stressed rats treated with tianeptine, and tianeptine also reversed the decreases in CAT activity in stressed rats treated with saline, suggesting that tianeptine exerted antioxidant activity. In conclusion, the present findings open new vistas on the pharmacological activity of tianeptine, in particular, concerning its ability to attenuate oxidative stress.
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Acta Diabetologica - Increased prevalence of mood disorders and suicidal ideation in type 2 diabetic patients
Luciane Ceretta, Gislaine Réus, Helena Abelaira, Luciano Jornada, Mágada Schwalm, Neiva Hoepers, Cristiane Tomazzi, Karina Gulbis, Renan Ceretta e João Quevedo
This study evaluated the association of mood disorders, suicidal ideation and the quality of life in patients with type 2 diabetes. We used a case-control study employing 996 patients suffering with type 2 diabetes (using insulin for over 1 year), and 2.145 individuals without diabetes. The groups were then used to evaluate the presence of different mood disorders and suicidal ideation, beyond quality of life. In addition to this, fasting glucose and glycosylated hemoglobin (Hb1C) were also evaluated. The data were analyzed using the Pearson chi-squared test, logistic regression, ANCOVA and Student's t-tests. We showed an association between type 2 diabetes and depressive episodes (adjusted OR = 1.8, CI 95 % 1.7-2.0, p < 0.001), recurrent depressive episodes (adjusted OR = 2.4, CI 95 % 2.2-2.6, p < 0.001), dysthymia (adjusted OR = 5.2, CI 95 % 4.9-5.5, p < 0.001), mood disorder with psychotic symptoms (adjusted OR = 2.5, CI 95 % 1.5-3.4, p < 0.001) and suicidal ideation (adjusted OR = 3.6, CI 95 % 2.5-4.8, p < 0.001, light; adjusted OR = 4.6, CI 95 % 1.5-7.7, p < 0.01, moderate and severe). The recurrent depression (OR = 1.3, CI 95 % 1.1-1.7, p < 0.05) and psychotic symptoms (OR = 4.1, CI 95 % 1.1-15.1, p < 0.05) were associated with higher levels of Hb1C. Dysthymia was associated with high blood glucose (OR = 1.6, CI 95 % 1.1-2.5, p < 0.05). Patients had lower mean scores in the following domains: physical [36.5 (13.6) × 56.0 (4.9), p < 0.001)], psychological [42.6 (8.6) × 47.9 (8.6), p < 0.001] and environmental [40.0 (8.6) × 49.3 (8.3), p < 0.001], but had higher scores in the area of social relations [50.2 (16.9) × 35.7 (27.9), p < 0.001]. The data demonstrated a worse quality of life, a high comorbidity of type 2 DM with depressive disorders and suicidal ideation. In addition, the poor control of DM is associated with the severity of mood disorders.
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Neuroscience - Effects in the Regulation of Neurochemical Factors in an Animal Model Of Parkinson's Disease
Talita Tuon, Samira Valvassori, Jéssica Borges, Thaís Luciano, Camila Trom, Luciano Silva, João Quevedo, Claudio Souza, Fabio Lira e Ricardo Pinho
The effect of physical training on the neurochemical and oxidative stress markers were evaluated in the striatum of rats with Parkinson's disease (PD). Untrained+sham-operated (USO), untrained+PD (UPD), trained+sham-operated (TSO), and trained+PD (TPD) were submitted to training on the treadmill. The PD was induced and seven days after the lesion, the animals underwent a rotational test and euthanasia by decapitation. The striatum was homogenized for Western Blot with anti-tyrosine hydroxylase(TH), anti-brain-derived neurotrophic factor (BDNF), anti-alpha-synuclein, anti-sarcoplasmic reticulum Ca(2+)-ATPase (SERCAII), anti-superoxide dismutase (SOD), anti-catalase (CAT), anti-glutathione peroxidase (GPX), and specific buffer for oxidative damage (TBARS and carbonyl content). The UPD and TPD groups showed a clear rotational asymmetry, apart from a significant reduction in the level of TH, BDNF, alpha-synuclein, SOD, CAT, and GPX as well as an increase in the TBARS and carbonyl content, as observed in the UPD group. The TH level was not significantly altered but the TPD group increased the levels of BNDF, SERCA II, SOD, and CAT and decreased the oxidative damage in lipids and protein. The effects of exercise on PD indicate the possibility that exercise, to a certain extent, modulates neurochemical status in the striatum of rats, possibly by improving the oxidative stress parameters.
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Pharmacology, Biochemistry, and Behavior - Lithium and valproate modulate energy metabolism in an animal model of mania induced by methamphetamine
Gustavo Feier, Samira Valvassori, Roger Varela, Wilson Resende, Daniele Bavaresco, Meline Morais, Lis Mello-Santos, Mônica Levy Andersen, Emilio Streck e João Quevedo
Studies have shown alterations in mitochondrial complexes of bipolar disorder (BD) patients. However, changes in the Krebs cycle enzymes have been little studied. The animal model of mania induced by amphetamine has been widely used for the study of bipolar mania. The aim of this study is to assess behavioral and energy metabolism changes in an animal model of mania induced by methamphetamine (m-AMPH). Wistar rats were first given m-AMPH or saline for 14days, and then, between days 8 and 14, rats were treated with lithium (Li), valproate (VPA), or saline (Sal). Locomotor behavior was assessed using the open-field task and activities of Krebs cycle enzymes (citrate synthase and succinate dehydrogenase), mitochondrial respiratory chain complexes (I, II, III, and IV), and creatine kinase measured in the brain structures (prefrontal, amygdala, hippocampus, and striatum). Li and VPA reversed m-AMPH-induced hyperactivity. The administration of m-AMPH inhibited the activities of Krebs cycle enzymes and complexes of the mitochondrial respiratory chain in all analyzed structures. Li and VPA reversed m-AMPH-induced energetic metabolism dysfunction; however, the effects of Li and VPA were dependent on the brain region analyzed. From the results obtained in this study, we suggested that the decreased Krebs cycle enzymes activity induced by m-AMPH may be inhibiting mitochondrial respiratory chain complexes. Therefore, changes in the Krebs cycle enzymes may also be involved in BD.
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