title: Oxytocin modulates GABAAR subunits to confer neuroprotection in stroke in vitro.
abstract: Oxytocin protects against ischemia-induced inflammation and oxidative stress, and is associated with GABA (γ-aminobutyric acid, an inhibitory neurotransmitter) signaling transduction in neurons. However, the molecular mechanism by which oxytocin affords neuroprotection, especially the interaction between oxytocin receptor and GABAAreceptor (GABAAR), remains to be elucidated. Primary rat neural cells were exposed to oxytocin before induction of experimental acute stroke model via oxygen-glucose deprivation-reperfusion (OGD/R) injury. Pretreatment with oxytocin increased cell viability, decreased the cell damage against oxidative stress, and prevented the release of high mobility group box1 during OGD/R. However, introduction of oxytocin during OGD/R did not induce neuroprotection. Although oxytocin did not affect the glutathione-related cellular metabolism before OGD, oxytocin modulated the expression levels of GABAAR subunits, which function to remove excessive neuronal excitability via chloride ion influx. Oxytocin-pretreated cells significantly increased the chloride ion influx in response to GABA and THIP (δ-GABAAR specific agonist). This study provides evidence that oxytocin regulated GABAAR subunits in affording neuroprotection against OGD/R injury.
authors: Center of Excellence for Aging and Brain, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, 12901 Bruce B Downs Blvd, Tampa FL 33612, USA.
authors: Yuji
authors: Y
authors: Kaneko
authors: School of Aging Studies, University of South Florida, 13301 Bruce B Downs Blvd, Tampa FL 33612, USA.
authors: Colleen
authors: C
authors: Pappas
authors: Center of Excellence for Aging and Brain, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, 12901 Bruce B Downs Blvd, Tampa FL 33612, USA.
authors: Naoki
authors: N
authors: Tajiri
authors: Center of Excellence for Aging and Brain, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, 12901 Bruce B Downs Blvd, Tampa FL 33612, USA.
authors: Cesar V
authors: CV
authors: Borlongan
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D007700:Kinetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010121:Oxytocin / Q000494:pharmacology*; D021122:Protein Subunits; D051381:Rats; D011963:Receptors, GABA-A / Q000737:chemistry / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D015398:Signal Transduction / Q000187:drug effects; D020521:Stroke / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*
chemical_list: D002712:Chlorides; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D018696:Neuroprotective Agents; D021122:Protein Subunits; D011963:Receptors, GABA-A; D010121:Oxytocin; D019803:Glutathione Disulfide