Related Experiment Video
Updated: Mar 27, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglia antioxidant systems and redox signalling
F Vilhardt, J Haslund-Vinding1,2, V Jaquet2
1Institute of Cellular and Molecular Medicine, Copenhagen University, Copenhagen, Denmark.
Abstract:
For many years, microglia, the resident CNS macrophages, have been considered only in the context of pathology, but microglia are also glial cells with important physiological functions. Microglia-derived oxidant production by NADPH oxidase (NOX2) is implicated in many CNS disorders. Oxidants do not stand alone, however, and are not always pernicious. We discuss in general terms, and where available in microglia, GSH synthesis and relation to cystine import and glutamate export, and the thioredoxin system as the most important antioxidative defence mechanism, and further, we discuss in the context of protein thiolation of target redox proteins the necessity for tightly localized, timed and confined oxidant production to work in concert with antioxidant proteins to promote redox signalling. NOX2-mediated redox signalling modulates the acquisition of the classical or alternative microglia activation phenotypes by regulating major transcriptional programs mediated through NF-κB and Nrf2, major regulators of the inflammatory and antioxidant response respectively. As both antioxidants and NOX-derived oxidants are co-secreted, in some instances redox signalling may extend to neighboring cells through modification of surface or cytosolic target proteins. We consider a role for microglia NOX-derived oxidants in paracrine modification of synaptic function through long term depression and in the communication with the adaptive immune system. There is little doubt that a continued foray into the functions of the antioxidant response in microglia will reveal antioxidant proteins as dynamic players in redox signalling, which in concert with NOX-derived oxidants fulfil important roles in the autocrine or paracrine regulation of essential enzymes or transcriptional programs.
Linked Articles:
This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc.
Insights
Microglia utilize NADPH oxidase (NOX2) to produce oxidants that, along with antioxidant systems, regulate redox signaling. This signaling influences microglia activation, synaptic function, and immune communication, highlighting their physiological roles beyond pathology.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Microglia, the brain's resident macrophages, possess crucial physiological functions beyond their known roles in pathology.
- NADPH oxidase (NOX2)-derived oxidants from microglia are implicated in central nervous system (CNS) disorders.
- Oxidants and antioxidants, including glutathione (GSH) and the thioredoxin system, interact dynamically within cells.
Purpose of the Study:
- To explore the physiological roles of microglia in redox signaling.
- To elucidate the interplay between microglial oxidant production and antioxidant defense mechanisms.
- To understand how NOX2-mediated redox signaling regulates microglial activation and function.
Main Methods:
- Discussion of GSH synthesis, cystine import/glutamate export, and the thioredoxin system in microglia.
- Analysis of protein thiolation and its role in redox signaling.
- Examination of NOX2-mediated regulation of NF-κB and Nrf2 transcriptional programs.
Main Results:
- NOX2-derived oxidants and antioxidant systems work in concert to promote redox signaling.
- Redox signaling modulates microglial activation phenotypes (classical/alternative) via NF-κB and Nrf2.
- Microglial oxidants can mediate paracrine effects on synaptic function and immune cell communication.
Conclusions:
- Microglial antioxidant proteins are dynamic regulators of redox signaling.
- NOX2-derived oxidants and antioxidant proteins collaborate in autocrine and paracrine signaling.
- Microglia play vital physiological roles in regulating CNS function through redox signaling.
