Sodium butyrate abolishes lipopolysaccharide-induced depression-like behaviors and hippocampal microglial activation in mice

Yosuke Yamawaki, Norika Yoshioka, Kanako Nozaki, Hikaru Ito, Keisuke Oda, Kana Harada, Satomi Shirawachi, Satoshi Asano, Hidenori Aizawa, Shigeto Yamawaki, Takashi Kanematsu, Hiroyuki Akagi

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Patients with major depressive disorder have elevated peripheral inflammation; the degree of this increase correlates with the severity of the disorder. Chronic psychological stress increases pro-inflammatory cytokines and promotes microglial activation, leading to stress vulnerability. Epigenetics, including DNA methylation and histone modification, are also related to the pathophysiology of major depressive disorder. Sodium butyrate (SB), a histone deacetylase inhibitor, exerts an antidepressant effect by altering gene expression in the hippocampus. In this study, we investigated whether lipopolysaccharide (LPS)-induced depressive-like behaviors in mice are affected by the repeated treatment with SB. Intraperitoneal injection of LPS (5 mg/kg) induced cytokines and ionized calcium-binding adaptor molecule 1(Iba1), a marker of microglial activation, in the hippocampus. It also increased the immobility time in a forced swim test, without changing locomotion. Repeated treatment with SB reduced LPS-induced alterations. These findings suggested that epigenetic regulation exist in hippocampal microglial activation, and is involved in depressive-like behaviors associated with neuro-inflammation. Further, using cDNA microarray analyses, we examined whether LPS and SB treatment affected the microglial gene profiles. Our results indicated 64 overlapping genes, between LPS-increased genes and SB-decreased genes. Among these genes, EF hand calcium binding domain 1 was a particularly distinct candidate gene. Altogether, our findings indicated that microglial activation mediated through epigenetic regulation may be involved in depressive-like behaviors. In addition, we demonstrated the effect of SB on gene information in hippocampal microglia under neuroinflammatory conditions.

Original languageEnglish
Pages (from-to)13-38
Number of pages26
JournalBrain Research
Volume1680
DOIs
Publication statusPublished - Feb 1 2018

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Butyric Acid
Lipopolysaccharides
Depression
Epigenomics
Genes
Major Depressive Disorder
Hippocampus
Histone Code
Overlapping Genes
Cytokines
Inflammation
Calcium
EF Hand Motifs
Histone Deacetylase Inhibitors
Microglia
DNA Methylation
Locomotion
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Intraperitoneal Injections

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Sodium butyrate abolishes lipopolysaccharide-induced depression-like behaviors and hippocampal microglial activation in mice. / Yamawaki, Yosuke; Yoshioka, Norika; Nozaki, Kanako; Ito, Hikaru; Oda, Keisuke; Harada, Kana; Shirawachi, Satomi; Asano, Satoshi; Aizawa, Hidenori; Yamawaki, Shigeto; Kanematsu, Takashi; Akagi, Hiroyuki.

In: Brain Research, Vol. 1680, 01.02.2018, p. 13-38.

Research output: Contribution to journalArticle

Yamawaki, Y, Yoshioka, N, Nozaki, K, Ito, H, Oda, K, Harada, K, Shirawachi, S, Asano, S, Aizawa, H, Yamawaki, S, Kanematsu, T & Akagi, H 2018, 'Sodium butyrate abolishes lipopolysaccharide-induced depression-like behaviors and hippocampal microglial activation in mice', Brain Research, vol. 1680, pp. 13-38. https://doi.org/10.1016/j.brainres.2017.12.004
Yamawaki, Yosuke ; Yoshioka, Norika ; Nozaki, Kanako ; Ito, Hikaru ; Oda, Keisuke ; Harada, Kana ; Shirawachi, Satomi ; Asano, Satoshi ; Aizawa, Hidenori ; Yamawaki, Shigeto ; Kanematsu, Takashi ; Akagi, Hiroyuki. / Sodium butyrate abolishes lipopolysaccharide-induced depression-like behaviors and hippocampal microglial activation in mice. In: Brain Research. 2018 ; Vol. 1680. pp. 13-38.
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