title: Protective effects of salicylate on PKA inhibitor (H-89)-induced spatial memory deficit via lessening autophagy and apoptosis in rats.
abstract: In this study, the effects of salicylate on spatial learning and memory, through its effects on autophagy and apoptosis, were evaluated in the presence of the PKA inhibitor H-89. Adult male Wistar rats were divided into experimental groups as follows: salicylate (30, 50, 100μg/0.5μl/side, intra-hippocampal; 400mg/kg, intra-peritoneal), donepezil (1mg/kg as a positive control for behavioral effects of salicylate), H-89 (1μl/side of 5 or 20μM), H-89 plus salicylate and H-89 plus donepezil. The Morris water maze test was used for evaluation of spatial learning and memory. The levels of different apoptotic and autophagic biomarkers were evaluated using the western blot technique. Salicylate (100μg/0.5μl/side) significantly reduced the escape latency on training days, increased the percentage of time spent in the target quadrant during the probe trial and reversed the inhibitory effects of H-89 during the process of spatial learning and memory. The behavioral efficacy of salicylate was comparable to that of donepezil. In addition, salicylate significantly decreased the levels of apoptotic proteins, Bax and caspase 3, and increased the Bcl2 levels in all groups. Furthermore, the levels of LC3II and Atg7 were decreased by salicylate. Our study revealed that both systemic and direct intra-hippocampal administration of salicylate can facilitate the spatial learning and memory. Additionally, intra-hippocampal administration of salicylate can reduce apoptotic and autophagic proteins. The antioxidant activity of salicylate might lead to increased pCREB via stimulation of signaling pathways, resulting in reduction of H-89-induced apoptosis and autophagy.
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Azimi
authors.affiliation: Department of Toxicology and Pharmacology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Kachooeian
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Asal
authors.initials: A
authors.lastname: Yans
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Soomaayeh
authors.initials: S
authors.lastname: Heysieattalab
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Gelareh
authors.initials: G
authors.lastname: Vakilzadeh
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Nasim
authors.initials: N
authors.lastname: Vosoughi
authors.affiliation: Department of Toxicology and Pharmacology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Sanati
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Occupational Therapy, Faculty of Rehabilitation Sciences, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Ghorban
authors.initials: G
authors.lastname: Taghizadeh
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Toxicology and Pharmacology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: msharifzadeh@sina.tums.ac.ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sharifzadeh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D000071193:Autophagy-Related Protein 7 / Q000032:analysis; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D000077265:Donepezil; D004924:Escape Reaction / Q000187:drug effects; D007189:Indans / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D010766:Phosphorylation; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012459:Salicylates / Q000494:pharmacology*; D065852:Spatial Memory / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: C561242:Atg7 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D007189:Indans; D047908:Intracellular Signaling Peptides and Proteins; D007546:Isoquinolines; D010880:Piperidines; D012459:Salicylates; D013449:Sulfonamides; C015482:protein kinase modulator; D000077265:Donepezil; D000071193:Autophagy-Related Protein 7; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
keywords: Apoptosis; Autophagy; Hippocampus; PKA; Salicylate; Spatial memory