title: The involvement of protein kinase G inhibitor in regulation of apoptosis and autophagy markers in spatial memory deficit induced by Aβ.
abstract: The role of nitric oxide/protein kinase G (NO/PKG) in neurodegenerative disorders is controversial in different circumstances. PKG affects neurons both by itself and as a result of increased NO concentration. In this study, we examined the influence of PKG on spatial memory by intrahippocampal administration of three different concentrations of KT5823 as a PKG inhibitor. Morris water maze (MWM) was used for evaluation of behavioral alterations. We also measured the apoptosis and autophagy markers as two probable interfering pathways with PKG signaling by Western blot method. We found that in Aβ-pretreated rats, intrahippocampus infusions of 2.5, 5, and 10 μm/side of KT5823 led to a significant reduction in escape latency and traveled distance comparing to Aβ-treatment group. Our molecular findings indicated that KT5823 could induce autophagy and attenuate apoptotic markers at distinct doses. Here, we can conclude that in addition to other parameters, apoptosis, and autophagy in part have damaging and protective roles, respectively, in PKG signaling mechanisms. As autophagy-related proteins lose their functions in neurodegenerative diseases, we can suggest that autophagy can be one of the therapeutic aims for remedy of Alzheimer's disease.
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Marjan
authors.initials: M
authors.lastname: Shariatpanahi
authors.affiliation: NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
authors.affiliation: Department of Physiology, Physiology Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Ghorbangol
authors.initials: G
authors.lastname: Ashabi
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Behnoosh
authors.initials: B
authors.lastname: Bonakdar Yazdi
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shokoufeh
authors.initials: S
authors.lastname: Hassani
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Kian
authors.initials: K
authors.lastname: Azami
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abdollahi
authors.affiliation: Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Farshid
authors.initials: F
authors.lastname: Noorbakhsh
authors.affiliation: Department of Neuroscience, Faculty of Advanced Science and Technology in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ghorban
authors.initials: G
authors.lastname: Taghizadeh
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.|Department of Neuroscience, Faculty of Advanced Science and Technology in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sharifzadeh
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D002227:Carbazoles / Q000008:administration & dosage; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D057967:Infusions, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D010446:Peptide Fragments / Q000633:toxicity*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016229:Amyloid beta-Peptides; D002227:Carbazoles; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; C075222:amyloid beta-protein (1-42); C073601:KT 5823; D017869:Cyclic GMP-Dependent Protein Kinases
keywords: KT5823; Morris water maze; amyloid beta; autophagy; caspase-3; protein kinase G