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.

Detraining in pregnancy and/or lactation modulates neuropeptidergic hypothalamic systems in offspring mice.

Manipulations in metabolic parameters during pregnancy/lactation can impact the development of short- and long-term energy control mechanisms, which are mainly modulated by neural and hormonal inputs to the hypothalamus. Thus, we tested how mice training and detraining during pregnancy and lactation affect hypothalamus gene expression and change biometric and metabolic profiles of the offspring. Three-month-old female Swiss mice were submitted to an 8-week exercise program (swimming 5 times/week, 1 h/day). Following this physical exercise protocol, these conditioned animals and the control group were submitted to matting. After pregnancy verification, the animals were distributed into four groups: training during pregnancy and lactation (T); detraining after pregnancy confirmation (DP); detraining during lactation (DL); and control (CT), without interventions. After weaning, the offspring of the four groups were derived into these as follows: TO, DPO, DLO, and CTO, respectively. The body weight was lower in conditioned females compared to control at weeks 4-8 of the exercise regimen. No statistical difference in dam's body weight was observed during pregnancy. Related to offspring, at post-natal day 90, the animals were euthanized and DPO and DLO showed decrease in Npy and Cart expression in hypothalamus, and DLO also had increased Lep gene expression in white adipose tissue. Additionally, DPO showed increase in plasma triglycerides levels, total liver weight, and decrease in brown adipose tissue compared to CTO. Together, these results support that detraining during critical periods of development leads to altered gene expression in hypothalamic neuropeptidergic systems.

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 TNFα 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, TNFα, 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.