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Mediators of Inflammation
Volume 2015, Article ID 163140, 11 pages
Research Article

Histone Deacetylase Inhibitor Trichostatin A Ameliorated Endotoxin-Induced Neuroinflammation and Cognitive Dysfunction

1Department of Medical Research, Chi Mei Medical Center, Tainan 710, Taiwan
2Department of Anesthesiology, Chi Mei Medical Center, Tainan 710, Taiwan
3Department of Anesthesiology, Taipei Medical University, Taipei 110, Taiwan
4Department of Radiation Oncology, Buddhist Dalin Tzu Chi General Hospital, Chiayi 622, Taiwan
5School of Medicine, Tzu Chi University, Hualien 970, Taiwan
6Department of Surgery, Chi Mei Medical Center, Tainan 710, Taiwan
7Department of Medicinal Botanicals and Health Applications, Da-Yeh University, Changhua 515, Taiwan

Received 6 January 2015; Revised 25 March 2015; Accepted 25 March 2015

Academic Editor: Zhengyuan Xia

Copyright © 2015 Chung-Hsi Hsing et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Excessive production of cytokines by microglia may cause cognitive dysfunction and long-lasting behavioral changes. Activating the peripheral innate immune system stimulates cytokine secretion in the central nervous system, which modulates cognitive function. Histone deacetylases (HDACs) modulate cytokine synthesis and release. Trichostatin A (TSA), an HDAC inhibitor, is documented to be anti-inflammatory and neuroprotective. We investigated whether TSA reduces lipopolysaccharide- (LPS-) induced neuroinflammation and cognitive dysfunction. ICR mice were first intraperitoneally (i.p.) injected with vehicle or TSA (0.3 mg/kg). One hour later, they were injected (i.p.) with saline or Escherichia coli LPS (1 mg/kg). We analyzed the food and water intake, body weight loss, and sucrose preference of the injected mice and then determined the microglia activation and inflammatory cytokine expression in the brains of LPS-treated mice and LPS-treated BV-2 microglial cells. In the TSA-pretreated mice, microglial activation was lower, anhedonia did not occur, and LPS-induced cognitive dysfunction (anorexia, weight loss, and social withdrawal) was attenuated. Moreover, mRNA expression of HDAC2, HDAC5, indoleamine 2,3-dioxygenase (IDO), TNF-α, MCP-1, and IL-1β in the brain of LPS-challenged mice and in the LPS-treated BV-2 microglial cells was lower. TSA diminished LPS-induced inflammatory responses in the mouse brain and modulated the cytokine-associated changes in cognitive function, which might be specifically related to reducing HDAC2 and HDAC5 expression.