Microglia derived from aging mice exhibit an altered inflammatory profile

TLDR

Microglia are key players in neurodegenerative diseases and brain aging, yet their functional dynamics during aging remain poorly understood. The study aimed to evaluate the in vivo inflammatory responses of EGFP‑expressing microglia. This was achieved using young and aged transgenic mice expressing EGFP under the c‑fms promoter, with microglia sorted by flow cytometry. Aging microglia displayed lipofuscin accumulation, reduced process complexity, altered granularity, and elevated baseline expression of both pro‑ and anti‑inflammatory cytokines, and although LPS induced similar fold changes across ages, the sustained low‑level pro‑inflammatory cytokine production could influence brain aging. © 2007 Wiley‑Liss, Inc.

Abstract

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 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, altered granularity, and increased mRNA expression of both pro‐inflammatory (TNFα, IL‐1β, IL‐6) and anti‐inflammatory (IL‐10, TGFβ1) cytokines. Following lipopolysaccharide (LPS) challenge (1 mg/kg, 3 h), aging microglia exhibit increased basal expression of TNFα, IL‐1β, 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. © 2007 Wiley‐Liss, Inc.