title: Subchronic metformin pretreatment enhances novel object recognition memory task in forebrain ischemia: behavioural, molecular, and electrophysiological studies.
abstract: Metformin exerts its effect via AMP-activated protein kinase (AMPK), which is a key sensor for energy homeostasis that regulates different intracellular pathways. Metformin attenuates oxidative stress and cognitive impairment. In our experiment, rats were divided into 8 groups; some were pretreated with metformin (Met, 200 mg/kg) and (or) the AMPK inhibitor Compound C (CC) for 14 days. On day 14, rats underwent transient forebrain global ischemia. Data indicated that pretreatment of ischemic rats with metformin reduced working memory deficits in a novel object recognition test compared to group with ischemia-reperfusion (I-R) (P < 0.01). Pretreatment of the I-R animals with metformin increased phosphorylated cyclic-AMP response element-binding protein (pCREB) and c-fos levels compared to the I-R group (P < 0.001 for both). The level of CREB and c-fos was significantly lower in ischemic rats pretreated with Met + CC compared to the Met + I-R group. Field excitatory postsynaptic potential (fEPSP) amplitude and slope was significantly lower in the I-R group compared to the sham operation group (P < 0.001). Data showed that fEPSP amplitude and slope was significantly higher in the Met + I-R group compared to the I-R group (P < 0.001). Treatment of ischemic animals with Met + CC increased fEPSP amplitude and slope compared to the Met + I-R group (P < 0.01). We unravelled new aspects of the protective role of AMPK activation by metformin, further emphasizing the potency of metformin pretreatment against cerebral ischemia.
authors.affiliation: a Ahvaz Physiology Research Center and Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Ghorbangol
authors.initials: G
authors.lastname: Ashabi
authors.affiliation: a Ahvaz Physiology Research Center and Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Sarkaki
authors.affiliation: b Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
authors.affiliation: c Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Shima
authors.initials: S
authors.lastname: Zareh Shahamati
authors.affiliation: d Medical School, Alborz University of Medical Sciences, Karaj, Iran.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Goudarzvand
authors.affiliation: a Ahvaz Physiology Research Center and Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Yaghoob
authors.initials: Y
authors.lastname: Farbood
authors.affiliation: a Ahvaz Physiology Research Center and Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Badavi
authors.affiliation: d Medical School, Alborz University of Medical Sciences, Karaj, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Khalaj
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology; D060825:Cognitive Dysfunction / Q000188:drug therapy*; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000378:metabolism; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects*; D008687:Metformin / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D016548:Prosencephalon / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D007004:Hypoglycemic Agents; D018696:Neuroprotective Agents; D016760:Proto-Oncogene Proteins c-fos; D008687:Metformin; D055372:AMP-Activated Protein Kinases
keywords: AMPK; CREB; global cerebral ischemia; ischémie cérébrale globale; memory and learning; metformin; metformine; mémoire et apprentissage