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.

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 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 analysed 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 analysed 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.

Nesfatin-1 and neuronostatin neurons are co-expressed with glucocorticoid receptors in the hypothalamus.

Nesfatin-1 and neuronostatin in the central nervous system participate in regulating stress responses. Glucocorticoid hormones affect the brain through glucocorticoid receptors (GR). We investigated in the rat the possibility of co-localizing nesfatin-1 and neuronostatin neurons in hypothalamic areas with GR. using immunohistochemistry. We counted nesfatin-1 and neuronostatin stained neurons. We counted GR positive nesfatin-1 neurons in the arcuate nucleus (ARC) and paraventricular nucleus (PVN) and GR positive neuronostatin neurons in the periventricular nucleus (PeN). The percentage of nesfatin-1 neurons that expressed GR was 38.4% in female rats and 21.9% in male rats in the ARC, and 33.3% in female rats and 29.2% in male rats in the PVN. The percentage of neuronostatin neurons that expressed GR was 39.1% in female rats and 39.9% in male rats in the PeN. We found that a substantial portion of nesfatin-1 and neuronostatin neurons were stained for GR. We speculate that the pattern of GR might permit secretion of neuropeptides to be stimulated by peripheral glucocorticoid signals. Stress can suppress food intake, in part, through the GR in neurons that express nesfatin-1, which is a satiety molecule, and in neurons that express neuronostatin, which is an anorexigenic peptide.