title: SB203580 reverses memory deficits and depression-like behavior induced by microinjection of Aβ1-42into hippocampus of mice.
abstract: A high co-morbidity between Alzheimer's disease (AD) and depression suggests there might be similar mechanisms underlying the course of these diseases. Previous studies have shown that p38MAPK plays a critical role in the pathophysiology of AD and depression. However, little is known about whether SB203580, a selective inhibitor of p38MAPK, may protect against AD-associated cognitive impairments and depression-like behavior, simultaneously. Herein, we have shown, for the first time, that SB203580 may reverse memory impairments and depression-like behavior induced by hippocampal infusion of β-amyloid 1-42 (Aβ1-42), as measured by novel object recognition, Morris water maze, tail-suspension and forced-swimming tests. In addition, phorbol 12-myristate 13-acetate (PMA), a PKC activator which also activates p38MAPK, significantly abolished the effects of SB203580. Moreover, Aβ1-42causes increased phosphorylation of p38MAPK and decreased phosphorylation of Ser9-glycogen synthase kinase 3β (GSK3β) and cAMP-response element binding protein (CREB) in the hippocampus of mice, which could be significantly reversed by SB203580. Our results suggest that SB203580 reversed Aβ1-42-induced cognitive impairments and depression-like behavior via inhibiting p38MAPK signaling pathway, which not only supports p38MAPK as a therapeutic target for AD-associated cognitive dysfunction and depression-like behavior, but also provides experimental basis for the use of SB203580 in co-morbidity of AD and depression.
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Guo
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China.
authors.forename: Lan
authors.initials: L
authors.lastname: Chang
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China.
authors.forename: Chenli
authors.initials: C
authors.lastname: Li
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Li
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China.
authors.forename: Peiyun
authors.initials: P
authors.lastname: Yan
authors.affiliation: School of Medicine, Lishui University, Lishui, Zhejiang, 323000, People's Republic of China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. wangchuang@nbu.edu.cn.
authors.forename: Chuang
authors.initials: C
authors.lastname: Wang
authors.affiliation: The Affiliated Hospital of School of Medicine, Ningbo University, Ningbo, Zhejiang, 315200, China. zhaqin@nbu.edu.cn.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zha
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. wangqinwen@nbu.edu.cn.
authors.forename: Qinwen
authors.initials: Q
authors.lastname: Wang
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003863:Depression / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D008845:Microinjections; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; C075222:amyloid beta-protein (1-42); D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
keywords: Alzheimer’s disease; Depression; β-amyloid 1–42; p38MAPK