Regulation Of BDNF/TrkB Pathway By Apelin-13 In Rats With Chronic Stress Induced Memory Impairment And Activation Of Glial Cells In Hippocampus

[purpose of the research] Stress events are closely related to the health of the body.The cognitive impairment caused by stress and its pathophysiological mechanisms and prevention have become the focus of research in this field.Chronic stress can induce glial cells activation in the central nervous system to produce neuroinflammatory response,and central nervous system inflammation has an important relationship with animal space learning and memory impairment.BDNF can activate astrocytes through the related signaling pathway and Chronic stress can lead to down-regulation of BDNF expression.Apelin is a natural ligand of G protein-coupled receptor APJ.Apelin/APJ system is widely distributed in the central nervous system and Apelin-13 has the strongest biological activity in different length fragments produced by Apelin precursor peptide cleavage.Our previous studies showed that Apelin-13 can improve the acute forced swimming rats induced by the novel object recognition memory damage,Apelin-13 regulated by BDNF in hippocampus of GR nuclear translocation induced by chronic water immersion restraint stress depression behavior of rats.This study explores whether Apelin-13 improves the memory impairment and hippocampal glial cell activation by regulating the chronic immersion restraint stress(CWIRS)by regulating the BDNF/TrkB pathway.[method] Using novel object recognition experiment,Y maze experiment to observe the effects of intracerebroventricular microinjection of Apelin-13 on CWIRS induced memory impairment in rats;The effects of intracerebroventricular microinjection of Apelin-13 on the increase of integrated optical density(IOD)of GFAP or Iba-1 positive cells induced by CWIRS in rat hippocampus was observed by immunofluorescence.Western Blot was used to observe the effect of microinjection of Apelin-13 into the lateral ventricle on the down regulated expression of BDNF and pCREB in the hippocampus of rats induced by CWIRS.The novel object recognition test,Y maze and immunofluorescence technique was used to observe the effects of intraperitoneal injection of BDNF/TrkB pathway specific antagonist ANA-12 on rats,ANA-12 influence Apelin-13 to improve CWIRS induced the memory impairment and the increase of hippocampal GFAP or Iba-1 positive cells IOD.[Result] Apelin-13 can improve the recognition index of CWIRS induced novel object recognition and reduce the correct rate of Y maze.Apelin-13 Improves IOD Increased in CWIRS Induced Hippocampal GFAP or Iba-1 Positive Cells in Rats.Apelin-13 could improve the expression of BDNF and pCREB in hippocampus of rats induced by CWIRS.ANA-12 can block the effect of Apelin-13 on CWIRS induced neonatal recognition identification index,Y maze correct alternation rate and hippocampal GFAP or Iba-1 positive cell IOD increase.[conclusion] Apelin-13 regulation of BDNF/TrkB pathway improves memory impairment and hippocampal glial cell activation induced by chronic water immersion restraint stress in rats.