Subchronical treatment with Fluoxetine modifies the activity of the MCHergic and hypocretinergic systems. Evidences from peptide CSF concentration and gene expression

In the postero-lateral hypothalamus are located two neuronal systems that utilize the neuropeptides melanin-concentrating hormone (MCH) and hypocretins (also called orexins) as neuromodulators. These systems have reciprocal connections between them, and project throughout the central nervous system. MCH has been involved in the generation of sleep, mainly REM sleep, while hypocretins have a critical role in the generation of wakefulness. MCHergic activity is also involved in the pathophysiology of major depressive disorder (MD). In this regards, intracerebral administration of MCH promotes pro-depressive behaviors (i.e., immobility in the forced swimming test) and REM sleep hypersomnia, which is an important trait of depression. Furthermore, the antagonism of the MCHR-1 receptor has a reliable antidepressant effect, suggesting that MCH is a pro-depressive factor. Hypocretins have been also involved in mood regulation; however, their role in depression is still on debate. Taking these data into account, we explored whether systemic subchronical treatment with Fluoxetine (FLX), a serotonergic antidepressant, modifies the concentration of MCH in the cerebrospinal fluid (CSF), as well as the preproMCH mRNA expression. We also evaluated the hypocretinergic system by quantifying the hypocretin-levels in the CSF and the preprohypocretin mRNA expression. Compared to control, FLX increased the levels of preprohypocretin mRNA without affecting the hypocretin-1 CSF levels. On the contrary, FLX significantly decreased the MCH CSF concentration without affecting the preproMCH gene expression. This result is in agreement with the fact that MCH serum level diminishes during the antidepressant treatment in MD, and supports the hypothesis that an increase in the MCHergic activity could have pro-depressive consequences. (C) 2016 Brazilian Association of Sleep. Production and Hosting by Elsevier B.V.Proyecto de Cooperacion Bilateral Uruguay- Brasil, Dicyt-CNPqPrograma de Desarrollo de Ciencias Basicas (PEDECIBA)Associacao Fundo de Incentivo a Pesquisa (AFIP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Univ Fed Sao Paulo, Dept Psychobiol, Sao Paulo, BrazilUniv Republica, Dept Physiol, Sch Med, Montevideo, UruguayUniv Fed Sao Paulo, Dept Psychobiol, Sao Paulo, BrazilProyecto de Cooperacion Bilateral Uruguay- Brasil, Dicyt-CNPq: ANII-FCE-1-2011-1-5997Web of Scienc

24 bp duplication of CHIT1 gene and determinants of human chitotriosidase activity among participants of EPISONO, a population-based cross-sectional study, São Paulo, Brazil

Objectives: We investigated whether plasma chitotriosidase activity is related to Obstructive Sleep Apnea (OSA) conditions and is correlated with biochemical variables present in the EPISONO database. This is the first study conducted in an epidemiological and nutritional transition country using subjects from the EPISONO population-based cross-sectional study.Design and methods: Chitotriosidase (CHIT) activity was determined by fluorimetric assay. OSA classification was defined as an apnea-hypopnea index. the correlations were investigated using a multiple regression linear model and statistical criteria, with CHIT as the dependent variable and correlated variables (from the EPISONO database) as independent variables, to access the contribution of each one to the variation in CHIT activity.Results: No significant difference was observed when comparing the mean CHIT activities of different apnea groups. the prevalence of the CHIT1 24-bp duplication from patients with severe apnea was higher than in controls. in a multiple regression linear model, CHIT concentration was positively associated with age, creatine and testosterone. Age was the strongest predictor of CHIT variation, followed by gender, waist circumference and TNF alpha. levels. the whole regression model explained 14% of the CHIT variation.Conclusion: Many variables are related to CHIT activity and show evidence of the multifactor and potentially synergistic character of this enzyme. in this study, we found that age, gender, TNF alpha, Hcy, sleep efficiency and waist circumference were responsible for approximately 14% of CHIT variation. Further studies are needed to elucidate additional parameters that may be related to CHIT activity. (C) 2013 the Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)AFIPConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Psychobiol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Prevent Med, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Prevent Med, BR-04024002 São Paulo, BrazilWeb of Scienc

Cysteine A Potential Biomarker for Obstructive Sleep Apnea

Objective: Obstructive sleep apnea (OSA) is a risk factor for a number of cardiovascular conditions. Although homocysteine (Hey) and cysteine (Cys) are regarded as cardiovascular risk factors, few studies have analyzed Hey and Cys plasma concentrations in patients with OSA. the aim of this study was to evaluate the role of Hey and Cys in OSA in comparison with subjects without OSA and to determine the possible influence of obesity on these variables.Methods: Patients who submitted to polysomnography studies were recruited to engage in an 8-h fasting period for blood sample withdrawal, physical examination, ECG, and echocardiogram. A subgroup of lean patients with OSA (BMI <25 kg/m(2)) were analyzed to rule out the influence of obesity. Fifteen patients were randomly assigned to participate in a continuous positive airway pressure (CPAP) protocol to assess the influence of OSA treatment on the obtained measurements.Results: A total of 75 patients and 75 control subjects matched for age and sex were analyzed. the Cys plasma levels were higher in patients with OSA compared with control subjects (490.16 +/- 67.00 mu mol/L vs 439.81 +/- 76.12 mu mol/L, respectively, P < .01); however, the Hey plasma levels did not differ between groups. Cys plasma levels were also higher in the OSA lean subgroup when compared with lean control subjects (484.21 +/- 71.99 mu mol/L vs 412.01 +/- 70.73 mu mol/L, respectively, P = .009). There was a significant decrease of Cys plasma levels after 6 months of CPAP effective therapy.Conclusion: Cys is a potential biomarker of OSA in obese and nonobese patients and is reduced after effective OSA treatment. CHEST 2011; 139(2):246-252Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)AFIP-Associacao Fundo de Incentivo a Psicofarmacologia, São Paulo, BrazilNational Council for Scientific and Technological DevelopmentUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biosci, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biosci, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, São Paulo, BrazilFAPESP: 98/14303-3Web of Scienc