Abstract
Gap junctions serve as intercellular conduits that allow the exchange of small molecular weight molecules (up to 1 kDa) including ions, metabolic precursors and second messengers. Microglia are capable of recognizing peptidoglycan (PGN) derived from the outer cell wall of Staphylococcus aureus, a prevalent CNS pathogen, and respond with the robust elaboration of numerous pro-inflammatory mediators. Based on recent reports demonstrating the ability of tumor necrosis factor-α and interferon-γ to induce gap junction coupling in macrophages and microglia, it is possible that pro-inflammatory mediators released from PGN-activated microglia are capable of inducing microglial gap junction communication. In this study, we examined the effects of S. aureus-derived PGN on Cx43, the major connexin in microglial gap junction channels, and functional gap junction communication using single-cell microinjections of Lucifer yellow (LY). Exposure of primary mouse microglia to PGN led to a significant increase in Cx43 mRNA and protein expression. LY microinjection studies revealed that PGN-treated microglia were functionally coupled via gap junctions, the specificity of which was confirmed by the reversal of activation-induced dye coupling by the gap junction blocker 18-α-glycyrrhetinic acid. In contrast to PGN-activated microglia, unstimulated cells consistently failed to exhibit LY dye coupling. These results indicate that PGN stimulation can induce the formation of a functional microglial syncytium, suggesting that these cells may be capable of influencing neuroinflammatory responses in the context of CNS bacterial infections through gap junction intercellular communication.
Original language | English (US) |
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Pages (from-to) | 475-483 |
Number of pages | 9 |
Journal | Journal of Neurochemistry |
Volume | 95 |
Issue number | 2 |
DOIs | |
State | Published - Oct 2005 |
Externally published | Yes |
Keywords
- Central nervous system
- Connexin 43
- Gap junction
- Microglia
- Neuroinflammation
- Peptidoglycan
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience