title: ERK and p38 inhibitors attenuate memory deficits and increase CREB phosphorylation and PGC-1α levels in Aβ-injected rats.
abstract: In this study, we investigated the effect of intracerebroventricular administration of ERK and p38 specific inhibitors, U0126 and PD169316, respectively, on learning and memory deficits induced by amyloid beta (Aβ) in rats. To investigate the effects of these compounds on learning and memory, we performed Morris water maze (MWM) test. U0126 and/or PD169316 improved spatial learning in MWM in Aβ-injected rats, 20 days after Aβ-injection. To determine the mechanisms of action of U0126 and PD169316, we studies their effect on some intracellular signaling pathways such as Ca(+)/cAMP-response element binding protein (CREB), c-fos, and transcription factors that regulate mitochondrial biogenesis. Based on our data, CREB and c-fos levels decreased 7 days after Aβ-injection, while U0126 and/or PD169316 pretreatments significantly increased these levels. Moreover, U0126 and PD169316 activated peroxisome proliferator-activated receptor gamma coactivator-1a, nuclear respiratory factor 1, and mitochondrial transcription factor A, 7 days after Aβ-injection. Surprisingly, these factors were returned to vehicle level, 20 days after Aβ-injection. Our findings reinforce the potential neuroprotective effect of these inhibitors against the Aβ toxicity.
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Ghorbangol
authors.initials: G
authors.lastname: Ashabi
authors.forename: Mahmoudreza
authors.initials: M
authors.lastname: Ramin
authors.forename: Pegah
authors.initials: P
authors.lastname: Azizi
authors.forename: Zahra
authors.initials: Z
authors.lastname: Taslimi
authors.forename: Shabnam Zeighamy
authors.initials: SZ
authors.lastname: Alamdary
authors.forename: Abbas
authors.initials: A
authors.lastname: Haghparast
authors.forename: Niloufar
authors.initials: N
authors.lastname: Ansari
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Motamedi
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors; D000818:Animals; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology*; D008845:Microinjections; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051265:NF-E2-Related Factor 1 / Q000096:biosynthesis; D009570:Nitriles / Q000494:pharmacology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013238:Stereotaxic Techniques; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: D016229:Amyloid beta-Peptides; D002070:Butadienes; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D007093:Imidazoles; D051265:NF-E2-Related Factor 1; D009570:Nitriles; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016760:Proto-Oncogene Proteins c-fos; D016601:RNA-Binding Proteins; C489030:Tfam protein, rat; D014157:Transcription Factors; C113580:U 0126; D048051:p38 Mitogen-Activated Protein Kinases; C408604:2-(4-nitrophenyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazole