Inflammatory microglia are glycolytic and iron retentive and typify the microglia in APP/PS1 mice

Oct 25, 2017Brain, behavior, and immunity

Inflamed brain immune cells use sugar for energy, hold onto iron, and are common in Alzheimer’s model mice

AI simplified

Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗

Abstract

Primary microglia polarized with IFNγ showed a distinct increase in glycolysis associated with higher tumor necrosis factor-α (TNFα) expression.

Inflammatory microglia exhibited characteristic increases in TNFα and nitric oxide synthase 2 (NOS2) when polarized with IFNγ.
Glycolysis was found to be the main energy source for these polarized microglia, indicated by increased expression of the enzyme PFKFB3.
Increased intracellular iron retention in microglia was associated with elevated TNFα expression and enhanced glycolysis.
Transgenic APP/PS1 mice displayed genotype-related increases in glycolysis and ferritin expression compared to wildtype mice.
The findings suggest that inflammatory microglia have a unique metabolic signature that includes distinct iron handling profiles.

AI simplified

Microglia, like macrophages, can adopt inflammatory and anti-inflammatory phenotypes depending on the stimulus. In macrophages, the evidence indicates that these phenotypes have different metabolic profiles with lipopolysaccharide (LPS)- or interferon-γ (IFNγ)-stimulated inflammatory cells switching to glycolysis as their main source of ATP and interleukin-4 (IL-4)-stimulated cells utilizing oxidative phosphorylation. There is a paucity of information regarding the metabolic signatures of inflammatory and anti-inflammatory microglia. Here, we polarized primary microglia with IFNγ and show that the characteristic increases in tumor necrosis factor-α (TNFα) and nitric oxide synthase 2 (NOS2) were accompanied by increased glycolysis and an increase in the expression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB)3, an enzyme that plays a significant role in driving glycolysis. These changes were associated with increased expression of ferritin and retention of iron in microglia. Significantly, retention of iron in microglia increased TNFα expression and also increased glycolysis suggesting that increased intracellular iron concentration may drive the metabolic and/or inflammatory changes. Analysis of microglia prepared from wildtype mice and from transgenic mice that overexpress amyloid precursor protein (APP) and presenilin 1 (PS1; APP/PS1) revealed genotype-related increases in glycolysis, accompanied by increased PFKFB3, and an increase in the expression of ferritin. The data indicate a distinct metabolic signature of inflammatory microglia from APP/PS1 mice that are also distinguishable by their iron handling profiles.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Inflammatory microglia are glycolytic and iron retentive and typify the microglia in APP/PS1 mice

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief