LPS and TNF alpha modulate AMPA/NMDA receptor subunit expression and induce PGE2 and glutamate release in preterm fetal ovine mixed glial cultures

Weaver-Mikaere, Luke, Gunn, Alistair J., Mitchell, Murray D., Bennet, Laura and Fraser, Mhoyra (2013) LPS and TNF alpha modulate AMPA/NMDA receptor subunit expression and induce PGE2 and glutamate release in preterm fetal ovine mixed glial cultures. Journal of Neuroinflammation, 10 1: 153.1-153.13. doi:10.1186/1742-2094-10-153


Author Weaver-Mikaere, Luke
Gunn, Alistair J.
Mitchell, Murray D.
Bennet, Laura
Fraser, Mhoyra
Title LPS and TNF alpha modulate AMPA/NMDA receptor subunit expression and induce PGE2 and glutamate release in preterm fetal ovine mixed glial cultures
Journal name Journal of Neuroinflammation   Check publisher's open access policy
ISSN 1742-2094
Publication date 2013-12-17
Sub-type Article (original research)
DOI 10.1186/1742-2094-10-153
Open Access Status DOI
Volume 10
Issue 1
Start page 153.1
End page 153.13
Total pages 13
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Subject 2804 Cellular and Molecular Neuroscience
2808 Neurology
2403 Immunology
2800 Neuroscience
Formatted abstract
Background: White matter injury (WMI) is the major antecedent of cerebral palsy in premature infants, and is often associated with maternal infection and the fetal inflammatory response. The current study explores the therapeutic potential of glutamate receptor blockade or cyclooxygenase-2 (COX-2) inhibition for inflammatory WMI.

Methods: Using fetal ovine derived mixed glia cultures exposed to tumour necrosis factor-α (TNF-α) or lipopolysaccharide (LPS), the expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) and N-methyl D-aspartate (NMDA) glutamate receptors and their contribution to inflammation mediated pre-oligodendrocyte (OL) death was evaluated. The functional significance of TNF-α and COX-2 signalling in glutamate release in association with TNF-α and LPS exposure was also assessed.

Results: AMPA and NMDA receptors were expressed in primary mixed glial cultures on developing OLs, the main cell-type present in fetal white matter at a period of high risk for WMI. We show that glutamate receptor expression and configuration are regulated by TNF-α and LPS exposure, but AMPA and NMDA blockade, either alone or in combination, did not reduce pre-OL death. Furthermore, we demonstrate that glutamate and prostaglandin E2 (PGE2) release following TNF-α or LPS are mediated by a TNF-α-COX-2 dependent mechanism.

Conclusions: Overall, these findings suggest that glial-localised glutamate receptors likely play a limited role in OL demise associated with chronic inflammation, but supports the COX-2 pathway as a potential therapeutic target for infection/inflammatory-mediated WMI.
Keyword AMPA
COX-2
Fetal Sheep
in vitro
Inflammation
MK801
NBQX
NMDA
Pre-oligodendrocyte
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2014 Collection
 
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