Title

Early burst of glycolysis in microglia regulates mitochondrial dysfunction in oligodendrocytes under neuro-inflammation

Document Type

Conference Proceeding

Publication Date

5-2018

Publication Title

J Immunol

Abstract

Brain resident microglia plays a pathological role in the loss of oligodendrocyte's function under neuroinflammation. The precise signaling mechanism by which microglial driven factor attenuates the myelin gene expression under such condition is poorly defined. Here we used bioenergetic approach to understand the microglia-oligodendrocyte crosstalk. We found that mixed glial cells under inflammatory stimulation using lipopolysaccharide plus interferon gamma (LI) had significantly enhanced glycolysis with drastic attenuation of mitochondrial respiration and myelin gene expression. Dissecting the mixed glial culture into pure microglia, astrocyte and oligodendrocytes (OLs) revealed that primary microglia was the main source of higher glycolysis, inflammatory cytokines, and nitric oxide (NO). An early burst of glycolysis in microglia in response to LI treatment caused the production of inflammatory cytokines and NO, which is mediated by PDK1-Akt signaling. Culturing of OLs with LI-conditioned microglial media (mCM) resulted in complete failure of mitochondrial respiration in OLsalong with decreased expression of myelin genes. We identified that nitric oxide produced by microglia is the key player in the loss of mitochondrial respiration in OLs and targeting either glycolysis, PDK1 or Akt in microglia resulted in significant recovery of mitochondrial function and myelin genes expression in OLs. In summary, we identified a potential therapeutic signaling cascade in microglia; an early burst of glycolysis mediated by PDK1 and Akt, responsible for hyper-production of NO, ensuing in the failure of mitochondrial respiration in oligodendrocytes, and leading in reduction of myelin genes expression.

Volume

200

Issue

1 Suppl S

First Page

49.16

This document is currently not available here.

Share

COinS