Microglia derived from aging mice exhibit an altered inflammatory profile

Microglia play a critical role in neurodegenerative diseases and in the brain aging process. Yet, little is known about the functional dynamics of microglia during aging. Thus, using young and aging transgenic mice expressing enhanced-green fluorescent protein (EGFP) under the promoter of the c-fms gene for macrophage-colony stimulating factor receptor, we evaluated in vivo-induced inflammatory responses of EGFP-expressing microglia sorted by flow cytometry. Aging microglia were characterized by the presence of lipofuscin granules, decreased processes complexity, altere granularity, and increased mRNA expression of both proinflammatory (TNF alpha IL-beta, IL-6) and anti-inflammatory (IL-10, TGF beta 1) cytokines. Following lipopolysaccharide (LPS) challenge (1 mg/kg, 3 h), aging microglia exhibit increased basal expression of TNF alpha IL-10, IL-6, and IL-10. Yet, the fold-over-basal LPS response remained constant across age, implying that the inflammatory machinery in aging microglia is functional and adjusted to the basal state. Gender differences were not overall observed across the treatments (age, LPS). The low but sustained production of pro-inflammatory cytokines by aging microglia may have a profound impact in the brain aging process. (c) 2006 Wiley-Liss, Inc.