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Navegando Programa de Pós-graduação em Ciências Biológicas por Por Orientador "Colugnati, Diego Basile"
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Item Efeito neuroprotetor e antiepiléptico da infusão intracerebroventricular crônica de angiotensina-(1-7) em ratos com epilepsia do lobo temporal(Universidade Federal de Goiás, 2020-03-02) Gomes, Karina Pereira; Castro, Carlos Henrique de; http://lattes.cnpq.br/6354834854727314; Colugnati, Diego Basile; http://lattes.cnpq.br/3875833705952056; Colugnati, Diego Basile; Torres, Bruno Benetti Junta; Pedrino, Gustavo Rodrigues; Blanch, Graziela Torres; Menegatti, RicardoEpilepsy is a severe neurological disorder characterized by permanent predisposition of the brain to generate spontaneous and recurrent seizures. Temporal Lobe Epilepsy (TLE) is the most frequent type of epilepsy in adults and is often refractory to pharmacological treatments available. Recently, several neuropeptides and their receptors have been suggested as promising therapeutic targets for the treatment of epilepsy, including neuropeptides and receptors of the Renin Angiotensin System (RAS). The aim of this study was to evaluate the effects of chronic treatment with Angiotensin-(1-7) (Ang-(1-7)) in male Wistar rats with TLE. The Pilocarpine (PILO) model was used for TLE induction and after the first spontaneous seizure, the animals were submitted to stereotactic surgery for implant of a guide cannula attached to an osmotic minipump. Rats of control group (CT) underwent the same procedures as the rats of groups with epilepsy, but were resistant to PILO model, not developing ELT. Intracerebroventricular infusion of Ang-(1-7) (200ng/kg/h) or sterile saline solution (NaCl 0.9%) was performed for 30 days and body weight, feed intake and spontaneous seizures were evaluated. At the end of the treatment, behavioral tests were performed in Elevated Plus Maze (EPM) and Open Field (OF) for evaluation of anxiety-like behavior and locomotor/exploratory activity. In the next day after behavioral tests, the animals were euthanized and the hippocampus were dissected, stored and later processed for protein analysis using Western Blot technique. For RAS components investigation, protein levels of Angiotensin Converting Enzyme 2 (ACE2) and Neutral Endopeptidase (NEP), as well as AT1, AT2 and Mas receptors were evaluated. In addition, hippocampal levels of Interleukin-6 (IL-6), Superoxide Dismutase (SOD), Catalase (CAT), B-Cell Lymphoma 2 (Bcl-2) and the phosphorylation of Mammalian Target of Rapamycin (mTOR) were quantified. Chronic intracerebroventricular treatment with Ang-(1-7) significantly reduced the frequency of spontaneous epileptic seizures, mainly at light photoperiod of the light-dark cycle, without changing its duration. Saline treated TLE rats (EP) showed significantly lower body weight gain than control rats without epilepsy (CT), which was attenuated in the last two weeks by Ang- (1-7) treatment (EP + Ang-(1-7)). However, the feed intake did not differ among evaluated groups. The time spent in EPM open arms by EP group was significantly higher than CT group, an effect attenuated by Ang-(1-7) treatment. In addition, the total number of entries in EPM arms was higher in EP group, which was reversed in EP + Ang-(1-7) group. The number of crossings in OF was significantly higher in EP group, which was reversed by Ang-(1-7) treatment. However, the immobility time and the numbers of rearing, also increased in the EP group, were only attenuated by Ang-(1- 7) treatment. Our results, revealed that Ang-(1-7) positively regulated the antioxidant protein CAT, the anti-apoptotic protein Bcl-2 and also increased the phosphorylation of anti-apoptotic protein mTOR, all reduced by epilepsy in hippocampus. In addition, the upregulation of AT1 receptor induced by TLE in hippocampus was also attenuated by treatment with Ang-(1-7). The protein levels of ACE2, NEP and SOD enzymes, as well as AT2 receptor and IL-6 were not statistically different between the groups. Mas receptor was downregulated in hippocampus of EP + Ang-(1-7) group. Our data suggest that Ang-(1-7) has direct modifying effects on chronic TLE by reducing oxidative stress and hippocampal neuronal death. From these results we can conclude that chronic intracerebroventricular treatment with Ang-(1-7) in rats with PILO induced- TLE reduces hippocampal neuronal damage and the frequency of spontaneous seizures, attenuating the damage in body weight gain and behavioral abnormalities. This study provides evidence that Ang-(1-7) and its receptor are promising targets for the treatment of TLE and its comorbidities.Item Caracterização e avaliação de apneias obstrutivas induzidas em ratos com epilepsia e seu impacto no sono, respostas cardiovasculares e de esforço respiratório(Universidade Federal de Goiás, 2020-02-28) Lima Júnior, Cláudio Quintino de; Pansani, Aline Priscila; http://lattes.cnpq.br/6385679829734771; Colugnati, Diego Basile; http://lattes.cnpq.br/3875833705952056; Colugnati, Diego Basile; Pansani, Aline Priscila; Rosa, Daniel Alves; Costa, Renata MazaroEpilepsy is one of the most common neurological diseases. Mortality rates are considerably higher in individuals with epilepsy and the most common category of death related is Sudden Unexpected Death in Epilepsy (SUDEP). Multifactorial mechanisms related to autonomic and respiratory cardiac changes underlying SUDEP. Obstructive sleep apnea (OSA) has a high incidence in patients with epilepsy and it is a risk factor for SUDEP. The aim of this study was to characterize OSA in animals with epilepsy. For this, Wistar rats (230-250g) were submitted to Pilocarpine model of epilepsy. After 30-60 days of chronic epilepsy, the animals were submitted to surgical procedures to evaluation of sleep and heart rate, respiratory effort and induction of obstructive apneas. Rats with epilepsy had altered basal sleep, with decreasing REM in 24-hour record and increased wakefulness and decreased NREM sleep in the dark phase of the cycle. Both NREM and REM sleep of these rats had a higher percentage of delta waves, and REM had lower theta waves. Rats with epilepsy had higher spontaneous central sleep apneas. Control rats had REM-sleep apneas longer than NREM-sleep apneas. This difference did not occur in rats with epilepsy. OSA did not altered sleep fraction in any group. In Epilepsy group, there was decrease in REM fraction at the first 8 h of recovery sleep of REM-apneas. Cardiovascular and respiratory effort during OSA and chemoreflex response were similar between groups. However, in epilepsy, there was a tendency to low in both respiratory effort in awake apneas and pressure response induced bychemoreflex. In epilepsy, there was higher density of NK1 in pré-Bötzinger and lower number of serotonergic neurons in Raphe Magnus and Pallidus. Therefore, rats with epilepsy had alteration on sleep-wake cycle and in sleep-delta/theta ratio. Also, the mechanisms related to end of OSA were altered, possibly by alteration in neurons of respiratory control.