Glutamate receptor antagonist suppresses the activation of nesfatin-1 neurons following refeeding or glucose administration

Background: Nesfatin-1 is a newly identified satiety peptide that has regulatory effects on food intake and glucose metabolism, and is located in the hypothalamic nuclei, including the supraoptic nucleus (SON). In this study, we have investigated the hypothesis that nesfatin-1 neurons are activated by refeeding and intraperitoneal (ip) glucose injection and that the glutamatergic system has regulatory influences on nesfatin-1 neurons in the SON. Materials and methods: The first set of experiments analyzed activation of nesfatin-1 neurons after refeeding as a physiological stimulus and the effectiveness of the glutamatergic system on this physiological stimulation. The subjects were randomly divided into three groups: fasting group, refeeding group and antagonist (CNQX+refeeding) group.  The second set of experiments analyzed activation of nesfatin-1 neurons by glucose injection as a metabolic stimulus and the effectiveness of the glutamatergic system on this metabolic stimulation. The subjects were randomly divided into three groups: saline group, glucose group and antagonist (CNQX+glucose) group. Results: Refeeding significantly increased the number of activated nesfatin-1 neurons by approximately 66%, and intraperitoneal glucose injection activated these neurons by about 55%, compared to the fasting and saline controls. The injections of glutamate antagonist (CNQX) greatly decreased the number of activated nesfatin-1 neurons. Conclusions: This study suggested that nesfatin-1 neurons were activated by peripheral and/or metabolic signals and that this effect was mediated through the glutamatergic system

Expression of the ionotropic glutamate receptors on neuronostatin neurons in the periventricular nucleus of the hypothalamus

Background: Neuronostatin, a newly identified peptide, is accepted as an anorexigenic peptide since it suppresses food intake when given intracerebroventricularly. Although the effect mechanisms of neuronostatin have been shown in different studies, there are no reports in the literature describing the mechanisms controlling neuronostatin neurons. In this study, we aimed to determine the presence of the ionotropic glutamate receptor subunits (iGluRs) in neuronostatin neurons in the periventricular nucleus of the hypothalamus. Materials and methods: The presence of glutamate receptors in neuronostatin neurons was investigated by dual immunohistochemistry. Immunohistochemistry was performed on 40 µm thick coronal brain sections with antibodies against AMPA (GluA1-4), kainate (GluK1/2/3, and GluK5), and NMDA (GluN1 and GluN2A) receptor subunits. Results: The results showed that the neuronostatin neurons expressed most of the NMDA and non-NMDA receptor subunits. The neuronostatin neurons in the anterior hypothalamic periventricular nucleus were particularly immunopositive for GluA1, GluA4, GluK1/2/3, GluK5 and GluN1 antibodies. No expression was observed for GluA2, GluA3 and GluN2A antibodies. Conclusions: For the first time in the literature, our study demonstrated that the neuronostatin neurons express glutamate receptor subunits which may form homomeric or heteromeric functional receptor complexes. Taken together, these results suggest that multiple subunits of iGluRs are responsible for glutamate transmission on neuronostatin neurons in the anterior hypothalamic periventricular nucleus

Testosterone Is Associated with Erectile Dysfunction: A Cross-Sectional Study in Chinese Men

Testosterone is essential for the regulation of erectile physiology, but the relationship between low testosterone and erectile dysfunction (ED) has not been firmly established.To examine the association between serum total, free and bio-available testosterone and ED in a population-based sample.A consecutive series of 1776 men aged 20–77 participated in the routine physical examination from September 2009 to December 2009 in Guangxi, China. ED was assessed using the five-item International Index of Erectile Function (IIEF-5) questionnaire. Total testosterone (TT), sex hormone binding globulin (SHBG) and other biochemical profiles were measured. Free testosterone (FT) and bio-available testosterone (BT) were calculated based on Vermeulen’s formula. Data were collected with regard to smoking, alcoholic drinking, physical activity and metabolic syndrome.The prevalence of ED (IIEF-5<22) was 47.6%. Men with ED were significantly older, and more prone to smoke cigarettes (≥20 cigarettes/day) or drink alcohol (≥3 drinks/week), and more likely to have elevated blood pressure (P = 0.036) or hyperglycemia (P<0.001) compared with those without ED. The significant increase in SHBG with age was parallel to its increase with increasing severity of ED (P<0.001). The obscure increase in TT across the ED status was detected without significance (P = 0.418), but TT was positively associated with ED after adjustment for age [odds ratio (OR)  = 1.02, 95% CI (confidence internal): 1.00–1.04]. FT and BT were inversely associated with ED (OR = 0.14, 95%CI: 0.06–0.33; OR = 0.92 (95%CI: 0.89–0.96, respectively) in the univariate analysis, and this inverse association appeared to be independent of smoking status, alcoholic drinking, physical activity, hyper-triglyceridemia and hyperglycemia.FT and BT are inversely related to worsening ED, whereas the positive association between TT and ED is most likely due to the increase in SHBG