Immunohistochemical Evidence for Glutamatergic Regulation of Nesfatin-1 Neurons in the Rat Hypothalamus


Gök Yurtseven Y. , Serter Koçoğlu S., Minbay Z. , Eyigor Ö.

BRAIN SCIENCES, vol.10, no.9, 2020 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 10 Issue: 9
  • Publication Date: 2020
  • Doi Number: 10.3390/brainsci10090630
  • Title of Journal : BRAIN SCIENCES
  • Keywords: glutamate, nesfatin-1, c-Fos, hypothalamus, rat, BLOOD-BRAIN-BARRIER, SUBUNIT MESSENGER-RNAS, C-FOS, RECEPTOR SUBUNITS, ULTRASTRUCTURAL-LOCALIZATION, SATIETY MOLECULE, KAINIC ACID, EXPRESSION, KAINATE, ACTIVATION

Abstract

Nesfatin-1, identified as an anorexigenic peptide, regulates the energy metabolism by suppressing food intake. The majority of nesfatin-1-synthesizing neurons are concentrated in various hypothalamic nuclei, especially in the supraoptic (SON), arcuate (ARC) and paraventricular nuclei (PVN). We tested the hypothesis that the glutamatergic system regulates nesfatin-1 neurons through glutamate receptors. Therefore, the first aim of the proposed studies was to examine effects of different glutamate agonists in the activation of nesfatin-1 neurons using c-Fos double immunohistochemical labeling. Experimental groups were formed containing male and female rats which received intraperitoneal injections of glutamate agonists kainic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) while the control rats received vehicle. The significant increase in the number of c-Fos-expressing nesfatin-1 neurons after agonist injections were observed both in female and male subjects and some of these effects were found to be sexually dimorphic. In addition, treatment with specific glutamate antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or dizocilpine (MK-801) before each of the three agonist injections caused a statistically significant reduction in the number of activated nesfatin-1 neurons in the hypothalamic nuclei including supraoptic, paraventricular and arcuate nuclei. The second aim of the study was to determine the expression of glutamate receptor subunit proteins in the nesfatin-1 neurons by using a double immunofluorescence technique. The results showed that the glutamate receptor subunits, which may form homomeric or heteromeric functional receptor channels, were expressed in the nesfatin-1 neurons. In conclusion, the results of this study suggest that nesfatin-1 neurons respond to glutamatergic signals in the form of neuronal activation and that the glutamate receptors that are synthesized by nesfatin-1 neurons may participate in the glutamatergic regulation of these neurons.