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
| Autor: | Jun Gu, Lulu Cao, Dan-Dan Yang, Xiao-Jie Zhao, Juan Ji, Xiu-Lan Sun, Ji-Ye Huang, Zhan Zhao, Ling Zhang |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Hypothalamo-Hypophyseal System endocrine system medicine.medical_specialty ATP-sensitive potassium channel Pituitary-Adrenal System Inflammation medicine.disease_cause 03 medical and health sciences 0302 clinical medicine KATP Channels Internal medicine Animals Medicine Chronic stress Neuroinflammation Propylamines biology Depression business.industry General Neuroscience medicine.disease Mice Inbred C57BL Oxidative Stress 030104 developmental biology Endocrinology Mood disorders Hypothalamus biology.protein Encephalitis medicine.symptom NeuN business Stress Psychological hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Brain Research Bulletin. 130:146-155 |
| ISSN: | 0361-9230 |
| DOI: | 10.1016/j.brainresbull.2017.01.026 |
| Popis: | Stress-induced disturbance of the hypothalamic-pituitary-adrenal (HPA) axis is strongly implicated in incidence of mood disorders. A heightened neuroinflammatory response and oxidative stress play a fundamental role in the dysfunction of the HPA axis. We have previously demonstrated that iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could prevent oxidative injury and neuroinflammation against multiple stimuli-induced brain injury. The present study was to demonstrate the impacts of Ipt in stress-induced HPA axis disorder and depressive behavior. We employed 2 stress paradigms: 8 weeks of continuous restraint stress (chronic restraint stress, CRS) and 2h of restraint stress (acute restraint stress, ARS), to mimic both chronic stress and severe acute stress. Prolonged (4 weeks) and short-term (a single injection) Ipt treatment was administered 30min before each stress paradigm. We found that HPA axis was altered after stress, with different responses to CRS (lower ACTH and CORT, higher AVP, but normal CRH) and ARS (higher CRH, ACTH and CORT, but normal AVP). Both prolonged and short-term Ipt treatment normalized stress-induced HPA axis disorders and abnormal behaviors in mice. CRS and ARS up-regulated mRNA levels of inflammation-related molecules (TNFα, IL-1β, IL-6 and TLR4) and oxidative stress molecules (gp91phox, iNOS and Nrf2) in the mouse hypothalamus. Double immunofluorescence showed CRS and ARS increased microglia activation (CD11b and TNFα) and oxidative stress in neurons (NeuN and gp91phox), which were alleviated by Ipt. Therefore, the present study reveals that Ipt could prevent against stress-induced HPA axis disorders and depressive behavior by alleviating inflammation and oxidative stress in the hypothalamus. |
| Databáze: | OpenAIRE |
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