title: Long-term dantrolene treatment reduced intraneuronal amyloid in aged Alzheimer triple transgenic mice.
abstract: In this study, we investigated the long-term treatment of dantrolene on amyloid and tau neuropathology, brain volume, and cognitive function in aged triple transgenic Alzheimer (3xTg-AD) mice. Fifteen-month old 3xTg-AD mice and wild-type controls were treated with oral dantrolene (5 mg/kg) or vehicle control twice a week for 6 months. Learning and memory were examined using the Morris Water Maze at 21 and 22 months of age. After the behavioral testing, hippocampal and cortical brain volumes were calculated with magnetic resonance imaging and motor function was evaluated using the rotorod. The amyloid burden and tau neurofibrillary tangles in the hippocampus were determined using immunohistochemistry. We found that dantrolene significantly decreased the intraneuronal amyloid accumulation by as much as 76% compared with its corresponding vehicle control, together with a trend to reduce phosphorylated tau in the hippocampus. No significant differences could be detected in hippocampal or cortical brain volume, motor function or cognition among all experimental groups, indicating that the mice were still presymptomatic for Alzheimer disease. Thus, presymptomatic and long-term dantrolene treatment significantly decreased the intraneuronal amyloid burden in aged 3xTg-AD mice before significant changes in brain volume, or cognition.
authors: Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.|Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Zhen
authors: Z
authors: Wu
authors: Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.|Department of Anesthesiology, First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200080, China.
authors: Bin
authors: B
authors: Yang
authors: Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.|Department of Anesthesiology, China-Japan Friendship Hospital, Beijing100029, China.
authors: Chunxia
authors: C
authors: Liu
authors: Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Ge
authors: G
authors: Liang
authors: Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Maryellen F
authors: MF
authors: Eckenhoff
authors: Small Animal Imaging Facility, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Weixia
authors: W
authors: Liu
authors: Small Animal Imaging Facility, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Stephen
authors: S
authors: Pickup
authors: Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Qingcheng
authors: Q
authors: Meng
authors: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Yuke
authors: Y
authors: Tian
authors: Department of Anesthesiology, First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200080, China.
authors: Shitong
authors: S
authors: Li
authors: Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Huafeng
authors: H
authors: Wei
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D003072:Cognition Disorders / Q000188:drug therapy; D003620:Dantrolene / Q000494:pharmacology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D008568:Memory / Q000187:drug effects*; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000188:drug therapy
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D003620:Dantrolene
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