title: Reduction of autophagy markers mediated protective effects of JNK inhibitor and bucladesine on memory deficit induced by Aβ in rats.
abstract: Autophagy, the process of self-degradation of cellular components, has an important role in neurodegenerative diseases, such as Alzheimer's disease. In this study, we investigated the effects of SP600125 as c-Jun N-terminal kinase (JNK) inhibitor and bucladesine as a cyclic adenosine 3',5'-monophosphate (cAMP) analog on spatial memory and expression of autophagic factors in Aβ-injected rats. Male Wistar rats were used. Rats were randomly allocated into five groups as following: amyloid beta (Aβ)-only group, Aβ + SP600125 (30 μg/1 μ/side, n = 7) and/or bucladesine (100 μM/1 μl/side, n = 7), and the normal control (vehicle only) group. The treatments were administered bilaterally to the CA1 sub-region of the hippocampus stereotaxically. Spatial reference memory was performed using Morris Water Maze 21 days later. The expression of authophagy markers (beclin1, Atg7, Atg12, and LC3 II/LC3 I) in the hippocampus was evaluated using western blotting. Compared to the vehicle group, Aβ administration reduced spatial reference learning (P < 0.001) and memory (P < 0.01) and upregulated the expression of beclin1, Atg7, Atg12, and LC3 II/I (P < 0.0001). Compare to Aβ-only group, the administration of SP600125 and/or bucladesine improved spatial reference learning (P < 0.001) and memory (P < 0.01). Compared to the Aβ-only group, the treatment with SP600125 and/or bucladesine also reduced beclin1, Atg7, Atg12, and LC3 II/I (P < 0.0001) which was similar to amount of normal rats. In summary, it seems that the improvement of spatial memory by SP600125 and/or bucladesine in Aβ-injected rats is in relation with normalizing of autophagy to the physiologic level, possibly through neuroprotection and/or neuroplasticity.
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Mohammadi
authors.affiliation: Liggins Institute, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand.|Centre for Brain Research, Faculty of Medicine and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand.|Gravida National Centre for Growth and Development, University of Auckland, Auckland, New Zealand.
authors.forename: J
authors.initials: J
authors.lastname: Guan
authors.affiliation: Neuroscience Research Centre, ShahidBeheshti University of Medical Sciences, Tehran, Iran.|Neurobiology Research Centre, ShahidBeheshti University of Medical Sciences, Tehran, Iran.
authors.forename: F
authors.initials: F
authors.lastname: Khodagholi
authors.affiliation: Neuroscience Research Centre, ShahidBeheshti University of Medical Sciences, Tehran, Iran.|Neurobiology Research Centre, ShahidBeheshti University of Medical Sciences, Tehran, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Yans
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.
authors.forename: S
authors.initials: S
authors.lastname: Khalaj
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Gholami
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.|Department of Neuroscience, Faculty of Advanced Science and Technology in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: G H
authors.initials: GH
authors.lastname: Taghizadeh
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, ShahidBeheshti University of Medical Sciences, Tehran, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Aliaghaei
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Abdollahi
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.
authors.forename: M H
authors.initials: MH
authors.lastname: Ghahremani
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran. msharifzadeh@tums.ac.ir.|Department of Neuroscience, Faculty of Advanced Science and Technology in Medicine, Tehran University of Medical Sciences, Tehran, Iran. msharifzadeh@tums.ac.ir.
authors.forename: M
authors.initials: M
authors.lastname: Sharifzadeh
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology / Q000627:therapeutic use*; D001343:Autophagy / Q000187:drug effects; D000071192:Autophagy-Related Protein 12 / Q000378:metabolism; D000071193:Autophagy-Related Protein 7 / Q000378:metabolism; D000071186:Beclin-1 / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar; D065852:Spatial Memory / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D000873:Anthracenes; D000071192:Autophagy-Related Protein 12; D000071193:Autophagy-Related Protein 7; D000071186:Beclin-1; D003994:Bucladesine; D048031:JNK Mitogen-Activated Protein Kinases; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; C561242:Atg7 protein, rat; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat; C432165:pyrazolanthrone
keywords: Alzheimer disease; Amyloid beta (Aβ); Autophagy; Bucladesine; SP600125