title: Glutamate microinjection into the hypothalamic paraventricular nucleus attenuates ulcerative colitis in rats.
abstract: OBJECTIVE
  To investigate the effects of glutamate microinjection into hypothalamic paraventricular nucleus (PVN) on ulcerative colitis (UC) in rats and to explore the relevant mechanisms.
  
  
  METHODS
  2,4,6-Trinitrobenzenesulfonic acid (100 mg/kg in 50% ethanol) was instilled into the colon of adult male SD rats to induce UC. A colonic damage score (CDS) was used to indicate the severity of the colonic mucosal damage. The pathological changes in the colonic mucosa were evaluated using immunohistochemistry, Western blotting, biochemical analyses or ELISA. Ten minutes before UC induction, drugs were microinjected into the relevant nuclei in rat brain to produce chemical stimulation or chemical lesion.
  
  
  RESULTS
  Microinjection of glutamate (3, 6 and 12 μg) into the PVN dose-dependently decreased the CDS in UC rats. This protective effect was eliminated after kainic acid (0.3 μg) was microinjected into PVN or into the nucleus tractus solitarius (NTS) that caused chemical lesion of these nuclei. This protective effect was also prevented when the AVP-V1 receptor antagonist DPVDAV (200 ng) was microinjected into the NTS. The discharge frequency of the vagus was markedly decreased following microinjection of glutamate into the PVN. Microinjection of glutamate into the PVN in UC rats significantly increased the cell proliferation and anti-oxidant levels, and decreased the apoptosis and Bax and caspase 3 expression levels and reduced the pro-inflammatory factors in the colonic mucosa.
  
  
  CONCLUSIONS
  The activation of hypothalamic PVN exerts protective effects against UC, which is mediated by the NTS and vagus. The effects may be achieved via anti-oxidative, anti-apoptotic, and anti-inflammatory factors.
authors.affiliation: 1] Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China [2] Department of Physiology, Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Ting-ting
authors.initials: TT
authors.lastname: Li
authors.affiliation: 1] Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China [2] Department of Physiology, Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Jian-fu
authors.initials: JF
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Su-juan
authors.initials: SJ
authors.lastname: Fei
authors.affiliation: 1] Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China [2] Department of Physiology, Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Sheng-ping
authors.initials: SP
authors.lastname: Zhu
authors.affiliation: 1] Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China [2] Department of Physiology, Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Jin-zhou
authors.initials: JZ
authors.lastname: Zhu
authors.affiliation: 1] Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China [2] Department of Physiology, Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Qiao
authors.affiliation: 1] Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China [2] Department of Physiology, Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Zhang-bo
authors.initials: ZB
authors.lastname: Liu
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D018698:Glutamic Acid / Q000494:pharmacology*; D008297:Male; D008845:Microinjections / Q000379:methods; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018698:Glutamic Acid