The role of microglial mtDNA damage in age-dependent prolonged LPS-induced sickness behavior

Hiroshi Nakanishi, Yoshinori Hayashi, Hiro Take

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Microglia are the main cellular source of oxidation products and inflammatory molecules in the brain during aging. The accumulation of mitochondrial DNA (mtDNA) oxidative damage in microglia during aging results in the increased production of reactive oxygen species (ROS). The increased intracellular ROS, in turn, activates a redox-sensitive nuclear factor-κB (NF-κB) to provoke excessive neuroinflammation, resulting in memory deficits and the prolonged behavioral consequence of infection. Besides its role in regulating the gene copy number, mitochondrial transcription factor A (TFAM) is closely associated with the stabilization of mtDNA structures. Lipopolysaccharide (LPS) induces the generation of ROS from the actively respirating mitochondria as well as NADPH oxidase, and leads to the subsequent activation of the NF-κB-dependent inflammatory pathway in aging microglia. The overexpression of human TFAM improves the age-dependent prolonged LPS-induced sickness behaviors by ameliorating the mtDNA damage and reducing the resultant redox-regulated inflammatory responses. Therefore, 'microglia-aging' plays important roles in the age-dependent enhanced behavioral consequences of infection.

Original languageEnglish
Pages (from-to)17-23
Number of pages7
JournalNeuron Glia Biology
Volume7
Issue number1
DOIs
Publication statusPublished - Jun 1 2012

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Illness Behavior
Microglia
Mitochondrial DNA
DNA Damage
Lipopolysaccharides
Reactive Oxygen Species
Oxidation-Reduction
Gene Dosage
NADPH Oxidase
Memory Disorders
Infection
Mitochondria
Brain

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Cellular and Molecular Neuroscience

Cite this

The role of microglial mtDNA damage in age-dependent prolonged LPS-induced sickness behavior. / Nakanishi, Hiroshi; Hayashi, Yoshinori; Take, Hiro.

In: Neuron Glia Biology, Vol. 7, No. 1, 01.06.2012, p. 17-23.

Research output: Contribution to journalArticle

Nakanishi, Hiroshi ; Hayashi, Yoshinori ; Take, Hiro. / The role of microglial mtDNA damage in age-dependent prolonged LPS-induced sickness behavior. In: Neuron Glia Biology. 2012 ; Vol. 7, No. 1. pp. 17-23.
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