Activation of ATP-sensitive potassium channel by iptakalim normalizes stress-induced HPA axis disorder and depressive behaviour by alleviating inflammation and oxidative stress in mouse hypothalamus.

摘要: Stress-induced disturbance of the hypothalamic-pituitary-adrenal (HPA) axis is strongly implicated in incidence mood disorders. A heightened neuroinflammatory response and oxidative stress play a fundamental role dysfunction HPA axis. We have previously demonstrated that iptakalim (Ipt), new ATP-sensitive potassium (K-ATP) channel opener, could prevent injury neuroinflammation against multiple stimuli-induced brain injury. The present study was to demonstrate impacts Ipt stress-induced disorder depressive behavior. employed 2 paradigms: 8 weeks continuous restraint (chronic stress, CRS) 2h (acute ARS), mimic both chronic severe acute stress. Prolonged (4 weeks) short-term (a single injection) treatment administered 30min before each paradigm. found altered after with different responses CRS (lower ACTH CORT, higher AVP, but normal CRH) ARS (higher CRH, AVP). Both prolonged normalized disorders abnormal behaviors mice. up-regulated mRNA levels inflammation-related molecules (TNFα, IL-1β, IL-6 TLR4) (gp91phox, iNOS Nrf2) mouse hypothalamus. Double immunofluorescence showed increased microglia activation (CD11b TNFα) neurons (NeuN gp91phox), which were alleviated by Ipt. Therefore, reveals behavior alleviating inflammation