Gastric distension activates NUCB2/nesfatin-1-expressing neurons in the nucleus of the solitary tract

Regul Pept. 2013 Nov 10:187:17-23. doi: 10.1016/j.regpep.2013.10.001. Epub 2013 Oct 10.

Abstract

Brainstem structures such as the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus nerve (DMNX) are essential for the digestive function of the stomach. A large number of neurotransmitters including glutamate and gamma-aminobutyric acid (GABA) are involved in the central control of gastric functions. However, the neuropeptidergic systems implicated in this process remain undetermined. Nesfatin-1 was recently identified as a neuropeptide cleaved from the N-terminal part of NEFA/nucleobindin 2 precursor (NUCB2). Central administration of this neuropeptide inhibits food consumption and gastroduodenal motility in rodents. Interestingly, the NTS and the DMNX contain a dense population of NUCB2/nesfatin-1 cell bodies. These observations led us to investigate the possible involvement of NUCB2/nesfatin-1 neurons in the brainstem neuronal pathways that modulate gastric functions. We observed an activation of NTS NUCB2/nesfatinergic neurons after gastric distention in rats. In addition, we found that several NTS NUCB2/nesfatinergic neurons were GABAergic. Finally, when fluorogold was injected at the stomach level, many retrogradely labeled neurons were observed in the DMNX which were also positive for NUCB2/nesfatin-1. Taken together, these observations suggest for the first time that NUCB2/nesfatin-1 neurons of the NTS are sensitive to gastric distension and then may contribute to the satiety signal.

Keywords: ChAT; DMNX; DVC; FG; Food intake; GABA; GAD67; GD; GI; GIN; Gastric distension; LPS; NTS; NUCB2; NUCB2/nesfatin-1; Nucleobindin-2; choline acetyltransferase; dorsal motor nucleus of the vagus nerve; dorsal vagal complex; eGFP-expressing Inhibitory Neurons; fluorogold; gamma amino-butyric acid; gastric distension; gastro-intestinal; glutamic acid decarboxylase 67; lipopolysaccharide; nucleus of the solitary tract.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Appetite Regulation*
  • Calcium-Binding Proteins / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Glutamate Decarboxylase / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism*
  • Nucleobindins
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Solitary Nucleus / cytology
  • Solitary Nucleus / physiology*
  • Stomach / innervation
  • Stomach / physiology*
  • Vagus Nerve / metabolism

Substances

  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • Nerve Tissue Proteins
  • Nucb1 protein, mouse
  • Nucb1 protein, rat
  • Nucleobindins
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1