Microglia derived from aging mice exhibit an altered inflammatory profile

Abstract

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 enhancedgreen 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, altered granularity, and increased mRNA expression of both proinflammatory (TNFa, IL-1b, IL-6) and anti-inflammatory (IL-10, TGFb1) cytokines. Following lipopolysaccharide (LPS) challenge (1 mg/kg, 3 h), aging microglia exhibit increased basal expression of TNFa, IL-1b, IL-6, and IL-10. Yet, the foldover-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. V V C 2006 Wiley-Liss, Inc.

Jmjd3 is essential for the epigenetic modulation of microglia phenotypes in the immune pathogenesis of Parkinson’s disease

“…38 Many lines of evidence have shown that aged microglia may give rise to altered inflammatory profiles with increased production of pro-inflammatory factors. [39][40][41][42] In aged mice as compared with young mice, treatment with MPTP can cause severe DA neuron loss and greater microglial activation in the SN. 43 It is possible that aged microglia is undergoing phenotype transformation by epigenetic modification.…”

Enhanced microglial pro‐inflammatory response to lipopolysaccharide correlates with brain infiltration and blood–brain barrier dysregulation in a mouse model of telomere shortening

“…We reasoned that telomere shortening could alter immune response in the presence of an external stimulus without changing the basal cellular profile drastically. Previously, aged microglia have been shown to display enhanced pro‐inflammatory activity in response to LPS (Sierra et al ., 2007). I.p.…”

Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

“…A chronic inflammatory response, identified by increases in ED1 + activated microglia, has been demonstrated repeatedly in the CNS of young animals months after irradiation (8,10,13,14). To date, however, experimental studies of radiation-induced inflammation, brain injury and cognitive dysfunction have been conducted almost exclusively in animals a few weeks to a few months old, young ages that do not reflect important neurobiological changes that occur with normal aging, such as decreased proliferation and neurogenesis (15)(16)(17)(18), increased microglial activation (19,20) and expression of pro-inflammatory cytokines (20)(21)(22). Experimental studies of stroke, traumatic brain injury, exogenous cytokine administration, and axotomy support the hypothesis that aging impacts the intensity and duration of brain inflammation and glial activation following challenges (23)(24)(25)(26)(27)(28).…”