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

作者：Lee Daniel C; Ruiz Claudia R; Lebson Lori; Selenica Maj Linda B; Rizer Justin; Hunt Jerry B Jr; Rojiani Rahil; Reid Patrick; Kammath Sidharth; Nash Kevin; Dickey Chad A; Gordon Marcia; Morgan Dave^*

来源：Neurobiology of Aging, 2013, 34(6): 1610-1620.

DOI：10.1016/j.neurobiolaging.2012.12.014

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

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)-alpha, interleukin (IL)-12, and IL-1 beta (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.

• 出版日期2013-6