Histone deacetylase inhibitor trichostatin a ameliorated endotoxin-induced neuroinflammation and cognitive dysfunction

Chung-Hsi Hsing, Shih Kai Hung, Yeong Chang Chen, Tsui Shan Wei, Ding Ping Sun, Jhi Joung Wang, Ching Hua Yeh

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article number163140
JournalMediators of Inflammation
Volume2015
DOIs
Publication statusPublished - 2015

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Histone Deacetylase Inhibitors
trichostatin A
Endotoxins
Lipopolysaccharides
Cytokines
Histone Deacetylases
Microglia
Cognition
Weight Loss
Brain
Indoleamine-Pyrrole 2,3,-Dioxygenase
Anhedonia
Inbred ICR Mouse
Anorexia
Cognitive Dysfunction
Interleukin-1
Drinking
Sucrose
Immune System
Anti-Inflammatory Agents

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

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Histone deacetylase inhibitor trichostatin a ameliorated endotoxin-induced neuroinflammation and cognitive dysfunction. / Hsing, Chung-Hsi; Hung, Shih Kai; Chen, Yeong Chang; Wei, Tsui Shan; Sun, Ding Ping; Wang, Jhi Joung; Yeh, Ching Hua.

In: Mediators of Inflammation, Vol. 2015, 163140, 2015.

Research output: Contribution to journalArticle

Hsing, Chung-Hsi ; Hung, Shih Kai ; Chen, Yeong Chang ; Wei, Tsui Shan ; Sun, Ding Ping ; Wang, Jhi Joung ; Yeh, Ching Hua. / Histone deacetylase inhibitor trichostatin a ameliorated endotoxin-induced neuroinflammation and cognitive dysfunction. In: Mediators of Inflammation. 2015 ; Vol. 2015.
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