Fasudil, an inhibitor of Rho-associated coiled-coil kinase, improves cognitive impairments induced by smoke exposure

Deng Xueyang; Ma Zhanqiang; Ma Chunhua; Hao Kun

doi:10.18632/oncotarget.12853

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Research Papers:

Fasudil, an inhibitor of Rho-associated coiled-coil kinase, improves cognitive impairments induced by smoke exposure

Deng Xueyang, Ma Zhanqiang, Ma Chunhua and Hao Kun _

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Oncotarget. 2016; 7:78764-78772. https://doi.org/10.18632/oncotarget.12853

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Abstract

Deng Xueyang1,*, Ma Zhanqiang1,*, Ma Chunhua1,3, Hao Kun2

1Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, China

2Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China

3Central Laboratory, Nanjing Municipal Hospital of T.C.M, The Third Affiliated Hospital of Nanjing University of T.C.M, Nanjing 210001, China

*These authors contributed equally to this work

Correspondence to:

Ma Chunhua, email: [email protected]

Hao Kun, email: [email protected]

Keywords: fasudil, smoke exposure, cognitive impairment, Rho/ROCK pathway

Received: August 25, 2016 Accepted: October 14, 2016 Published: October 24, 2016

ABSTRACT

The current study was designed to investigate the pathological changes in brain induced by smoke exposure, and explore whether fasudil could alleviate these impairments.

Adult C57BL/6 mice were exposed to tobacco smoking for four months, and fasudil was treated from the third months. To investigate lung injuries, the immunohistochemistry of lung tissue, immune cell infiltrations, cytokine productions in bronchoalveolar lavage (BAL) fluid, and seurm inflammatory cytokines were evaluated. To investigate cognitive impairments, Morris water maze test, hippocampal inflammatory cytokines and Rho associated signaling pathways were evaluated.

Our findings showed fasudil administration inhibited the inflitration of inflammatory cells (macrophages, neutrophils, and lymphocytes), suppressed the production of inflammatory cytokines both in the BAL fluid, serum, and hippocampus. Further, fasudil significantly improved the spatial learning and memory impairments and reduced the elevation of hippocampal inflammatory cytokines induced by tobacco smoking. Of note, expressions of RhoA, ROCK1, ROCK2, caspase-3, caspase-9, bax and the phosphorylation of NF-κBp65 were increased accompanying the smoke exposure-induced cognitive impairments, which were significantly inhibited by fasudil treatment as indicted in western blot and immunohistochemistry analysis.

Our results showed that fasudil exhibited protective effects on smoke exposure induced cognitive deficits which might involve with the regulation of Rho/ROCK/NF-κB pathways. Further studies are warranted before clinical application of fasudil.

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Research Papers:

Fasudil, an inhibitor of Rho-associated coiled-coil kinase, improves cognitive impairments induced by smoke exposure

Abstract