title: Geldanamycin Reduces Aβ-Associated Anxiety and Depression, Concurrent with Autophagy Provocation.
abstract: Neurodegenerative disorders are generally characterized by abnormal aggregation and deposition of specific proteins. Amyloid beta (Aβ)-associated neurodegenerative disorder is characterized by an oxidative damage that, in turn, leads to some behavioral changes before the establishment of dementia such as depression and anxiety. In the current study, we investigated the effect of heat shock protein 90 inhibitor geldanamycin (GA) administration 24 h before Aβ injection. In our experiment, 7 days after Aβ injection, elevated plus maze and forced swimming test were conducted to assess anxiety and depression-like behaviors. Levels of autophagy markers and malondialdehyde (MDA) and also activity of catalase in the hippocampus of rats were evaluated. Our behavioral analyses demonstrated that GA pretreatment can significantly decrease anxiety- and depression-like behaviors in Aβ-injected rats. Also, levels of autophagy markers including Atg12, Atg7, and LC3-II increased, while MDA level decreased and the activity of catalase increased in rats pretreated with GA compared to Aβ-injected rats. Thus, we assumed that GA, at least in part, ameliorated Aβ-mediated anxiety and depression by inducing autophagy and improving antioxidant defense system.
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Nayereh
authors.initials: N
authors.lastname: Zare
authors.affiliation: Medical Genomics Research Center and School of Advanced Sciences in Medicine, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran.
authors.forename: Solmaz
authors.initials: S
authors.lastname: Khalifeh
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|NeuroBiology 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.|NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Shima Zareh
authors.initials: SZ
authors.lastname: Shahamati
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Motamedi
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. nmaghsoudi@sbmu.ac.ir.|NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. nmaghsoudi@sbmu.ac.ir.
authors.forename: Nader
authors.initials: N
authors.lastname: Maghsoudi
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy*; D001343:Autophagy / Q000187:drug effects*; D016227:Benzoquinones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers; D002374:Catalase / Q000032:analysis; D003863:Depression / Q000139:chemically induced / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D005106:Exploratory Behavior / Q000187:drug effects; D005221:Fatigue / Q000139:chemically induced / Q000188:drug therapy; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D007276:Injections, Intraventricular; D047029:Lactams, Macrocyclic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018782:Maze Learning / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000037:antagonists & inhibitors*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D011292:Premedication; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming
chemical_list: D016229:Amyloid beta-Peptides; D016227:Benzoquinones; D015415:Biomarkers; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D008315:Malondialdehyde; D002374:Catalase; C001277:geldanamycin
keywords: Amyloid-β; Anxiety; Autophagy; Depression; Geldanamycin; HSP90