title: Aging enhances classical activation but mitigates alternative activation in the central nervous system.
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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Lee
authors.forename: Claudia R
authors.initials: CR
authors.lastname: Ruiz
authors.forename: Lori
authors.initials: L
authors.lastname: Lebson
authors.forename: Maj-Linda B
authors.initials: ML
authors.lastname: Selenica
authors.forename: Justin
authors.initials: J
authors.lastname: Rizer
authors.forename: Jerry B
authors.initials: JB
authors.lastname: Hunt
authors.forename: Rahil
authors.initials: R
authors.lastname: Rojiani
authors.forename: Patrick
authors.initials: P
authors.lastname: Reid
authors.forename: Sidharth
authors.initials: S
authors.lastname: Kammath
authors.forename: Kevin
authors.initials: K
authors.lastname: Nash
authors.forename: Chad A
authors.initials: CA
authors.lastname: Dickey
authors.forename: Marcia
authors.initials: M
authors.lastname: Gordon
authors.forename: Dave
authors.initials: D
authors.lastname: Morgan
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015398:Signal Transduction / Q000502:physiology