Neurodegeneration by activated microglia across a nanofiltration membrane

Microglia have been implicated in the pathogenesis of several neurodegenerative diseases, but their precise role remains elusive. Although neuron loss in the presence of lipopolysaccharide‐stimulated microglia has been well documented, a novel coculture paradigm was developed as a new approach to as...

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Bibliographic Details
Published in:Journal of biochemical and molecular toxicology 2012-02, Vol.26 (2), p.45-53
Main Authors: Graber, David J., Snyder-Keller, Abigail, Lawrence, David A., Turner, James N.
Format: Article
Language:English
Subjects:
Animals
Cell Survival
Cells, Cultured
Cellulose - analogs & derivatives
Cellulose - ultrastructure
Cellulose acetate
Coculture
Coculture Techniques - methods
Cytokines
Dopamine neuron
Dopaminergic Neurons - enzymology
Dopaminergic Neurons - pathology
Dopaminergic Neurons - physiology
Lipopolysaccharide
Lipopolysaccharides - pharmacology
Membranes, Artificial
Mesencephalon - cytology
Microglia - enzymology
Microglia - immunology
Microglia - metabolism
Neurodegenerative Diseases - pathology
NG-Nitroarginine Methyl Ester - pharmacology
Nitric Oxide - metabolism
Nitric Oxide - physiology
Nitric Oxide Synthase - antagonists & inhibitors
Nitric Oxide Synthase - metabolism
Rats
Rats, Sprague-Dawley
Tyrosine 3-Monooxygenase - metabolism
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Summary:Microglia have been implicated in the pathogenesis of several neurodegenerative diseases, but their precise role remains elusive. Although neuron loss in the presence of lipopolysaccharide‐stimulated microglia has been well documented, a novel coculture paradigm was developed as a new approach to assess the diffusible, soluble mediators of neurodegeneration. Isolated microglia were plated on membrane inserts that were coated with a layer of cellulose acetate. The cellulose acetate–coated membranes have nanofiltration properties, in that only molecules with masses less than 350 Da can pass through. Products released from activated microglia that were separated from primary ventral mesencephalon cells beneath the nanofiltering membrane were able to kill the dopamine neurons. Microglial cytokines cannot diffuse through this separating membrane. Addition of a nitric oxide synthase inhibitor prevented the loss of the dopamine neurons. These data describe a novel coculture system for studying diffusible factors and further support nitric oxide production as an important mediator in microglia‐induced neuron death. © 2011 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:45–53 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20384
ISSN:1095-6670
1099-0461
DOI:10.1002/jbt.20384