Related Experiment Videos
Microglial contribution to oxidative stress in Alzheimer's disease
C A Colton1, O N Chernyshev, D L Gilbert
1Department of Physiology, Georgetown University Medical School, Washington, DC 20007, USA. glia01@aol.com
Abstract:
Microglia are the CNS macrophage and are a primary cellular component of plaques in Alzheimer's disease (AD) that may contribute to the oxidative stress associated with chronic neurodegeneration. We now report that superoxide anion production in microglia or macrophages from 3 different species is increased by long term exposure (24 hours) to A beta peptides. Since A beta competes for the uptake of opsonized latex beads and for the production of superoxide anion by opsonized zymosan, a likely site of action are membrane receptors associated with the uptake of opsonized particles or fibers. The neurotoxic fibrillar peptides A beta (1-42) and human amylin increase radical production whereas a non-toxic, non-fibrillar peptide, rat amylin, does not. We also report that the effect of A beta peptides on superoxide anion production is not associated with a concomitant increase in nitric oxide (NO) production in either human monocyte derived macrophages (MDM) or hamster microglia from primary cultures. Since NO is known to protect membrane lipids and scavenge superoxide anion, the lack of A beta-mediated induction of NO production in human microglia and macrophages may be as deleterious as the over-production of superoxide anion induced by chronic exposure to A beta peptides.
Insights
Alzheimer's disease microglia and macrophages show increased superoxide anion production when exposed to amyloid beta peptides. This heightened radical production, without a corresponding increase in protective nitric oxide, may worsen neurodegeneration.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are central nervous system macrophages implicated in Alzheimer's disease (AD) pathology.
- Oxidative stress from microglia contributes to chronic neurodegeneration in AD.
Purpose of the Study:
- To investigate the effect of amyloid beta (A beta) peptides on superoxide anion production in microglia and macrophages.
- To determine if A beta-induced radical production impacts nitric oxide (NO) levels.
Main Methods:
- Primary cultures of microglia and human monocyte-derived macrophages (MDM) were exposed to A beta peptides for 24 hours.
- Superoxide anion and nitric oxide production were measured.
- Competition assays were used to identify potential A beta binding sites.
Main Results:
- Long-term exposure to fibrillar A beta (1-42) and human amylin increased superoxide anion production in microglia and macrophages.
- Non-fibrillar rat amylin did not increase radical production.
- A beta peptides did not increase nitric oxide production in human MDM or hamster microglia.
Conclusions:
- A beta peptides stimulate superoxide anion production in microglia and macrophages, potentially via membrane receptors involved in particle uptake.
- The lack of compensatory nitric oxide production alongside increased superoxide anion may exacerbate oxidative damage in Alzheimer's disease.