Aging enhances classical activation but mitigates alternative activation in the central nervous system

Daniel C. Lee, Claudia R. Ruiz, Lori Lebson, Maj Linda B. Selenica, Justin Rizer, Jerry B. Hunt, Rahil Rojiani, Patrick Reid, Sidharth Kammath, Kevin Nash, Chad A. Dickey, Marcia Gordon, Dave Morgan

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

The roles of microglia and macrophages during neuroinflammation and neurodegenerative diseases remain controversial. To date, at least 2 activations states have been suggested, consisting of a classical response (M1) and the alternative response (M2). Identifying selective biomarkers of microglia that representative their functional activation states may help elucidate disease course and enable a better understanding of repair mechanisms. Two cocktails containing either tumor necrosis factor (TNF)-α, interleukin (IL)-12, and IL-1β (referred to as CKT-1) or IL-13 and IL-4 (referred to CKT-2) were injections into the hippocampus of mice aged 6, 12, or 24 months. Microarray analysis was performed on hippocampal tissue 3 days postinjection. Gene transcripts were compared between CKT-1 versus CKT-2 stimulator cocktails. Several selective transcripts expressed for the CKT-1 included CXCL13, haptoglobin, MARCO, and calgranulin B, whereas a smaller subset of genes was selectively induced by the CKT-2 and consisted of FIZZ1, IGF-1, and EAR 11. Importantly, selective transcripts were induced at all ages by CKT-1, whereas selective gene transcripts induced by CKT-2 decreased with age suggesting an age-related reduction in the IL-4/ IL-13 signaling pathway.

Original languageEnglish
Pages (from-to)1610-1620
Number of pages11
JournalNeurobiology of Aging
Volume34
Issue number6
DOIs
StatePublished - Jun 2013

Keywords

  • Alternative activation
  • Classical activation
  • Cytokines
  • Inflammation
  • Macrophage
  • Microarray
  • Microglia

ASJC Scopus subject areas

  • Clinical Neurology
  • Geriatrics and Gerontology
  • Aging
  • General Neuroscience
  • Developmental Biology

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