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SB203580 reverses memory deficits and depression-like behavior induced by microinjection of Aβ1–42 into hippocampus of mice

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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, Aβ1–42 causes 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.

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Acknowledgments

This work was supported by National Natural Science Foundation of China (No. 81201050; No.81271209; U1503223); Natural Science Foundation of Zhejiang Province (No.LQ12H09001); Natural Science Foundation of Ningbo (No. 2012 A610249);Ningbo municipal innovation team of life science and health (2015C110026). This project also sponsored by K.C. Wong Magna funded at Ningbo University.

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  1. 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

    Jiejie Guo, Lan Chang, Chenli Li, Mengmeng Li, Peiyun Yan, Chuang Wang & Qinwen Wang

  2. School of Medicine, Lishui University, Lishui, Zhejiang, 323000, People’s Republic of China

    Zhiping Guo

  3. The Affiliated Hospital of School of Medicine, Ningbo University, Ningbo, Zhejiang, 315200, China

    Qin Zha

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  1. Jiejie Guo
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  3. Chenli Li
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Correspondence to Chuang Wang, Qin Zha or Qinwen Wang.

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Guo, J., Chang, L., Li, C. et al. SB203580 reverses memory deficits and depression-like behavior induced by microinjection of Aβ1–42 into hippocampus of mice. Metab Brain Dis 32, 57–68 (2017). https://doi.org/10.1007/s11011-016-9880-4

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