Geldanamycin Reduces Aβ-Associated Anxiety and Depression, Concurrent with Autophagy Provocation

• Published in: Journal of molecular neuroscience 2015-11, Vol.57 (3), p.317-324
• Main Authors: Zare, Nayereh, Khalifeh, Solmaz, Khodagholi, Fariba, Shahamati, Shima Zareh, Motamedi, Fereshteh, Maghsoudi, Nader
• Format: Article
• Language: English
• Subjects: Amyloid beta-Peptides - toxicity; Animals; Anxiety - chemically induced; Anxiety - drug therapy; Autophagy - drug effects; Benzoquinones - administration & dosage; Benzoquinones - pharmacology; Benzoquinones - therapeutic use; Biomarkers; Biomedical and Life Sciences; Biomedicine; Catalase - analysis; Cell Biology; Depression - chemically induced; Depression - drug therapy; Drug Evaluation, Preclinical; Exploratory Behavior - drug effects; Fatigue - chemically induced; Fatigue - drug therapy; Hippocampus - drug effects; Hippocampus - enzymology; HSP90 Heat-Shock Proteins - antagonists & inhibitors; Injections, Intraventricular; Lactams, Macrocyclic - administration & dosage; Lactams, Macrocyclic - pharmacology; Lactams, Macrocyclic - therapeutic use; Male; Malondialdehyde - blood; Maze Learning - drug effects; Nerve Tissue Proteins - analysis; Nerve Tissue Proteins - antagonists & inhibitors; Neurochemistry; Neurology; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurosciences; Oxidative Stress - drug effects; Premedication; Proteomics; Random Allocation; Rats; Rats, Wistar; Swimming
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-015-0619-1

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.