Cumiskey, D. and Butler, Marion P. and Moynagh, Paul N. and O'Connor, J.J.
(2007)
Evidence for a role for the group I metabotropic glutamate
receptor in the inhibitory effect of tumor necrosis factor-α
on long-term potentiation.
Brain Research, 1136.
pp. 13-19.
ISSN 0006-8993
Abstract
Pro-inflammatory cytokines are known to be elevated in several neuropathological states
that are associated with learning and memory. We have previously demonstrated in our
laboratory that the inhibition of long-term potentiation (LTP) in the dentate gyrus region of
the rat hippocampus, by tumor necrosis factor (TNF)-α, represents a biphasic response, an
early phase dependent on p38 mitogen activated protein kinase (MAPK) activation and a
later phase, possible dependent on protein synthesis. Many of the factors involved in the
early modulation of LTP by TNF-α have yet to be elucidated. This study investigated if
metabotropic glutamate receptors (mGluRs) are functionally linked to the inhibitory effect of
TNF-α on LTP in the rat dentate gyrus in vitro. We report that the impairment of early-LTP by
TNF-α is significantly attenuated by prior application of the group I/II mGluR antagonist
MCPG and more specifically the mGluR5 antagonist MPEP. Since TNF-α is now known to
cause transient increases in intracellular Ca2+ levels from ryanodine-sensitive stores, we
explored the possibility that disruption of intracellular Ca2+ homeostasis could be involved.
Ryanodine was found to significantly reverse the inhibition of LTP by TNF-α. From these
studies we propose that the TNF-α inhibition of LTP is dependent upon the activation of
TNFR1 and mGlu5-receptors. Importantly this study provides the first proof of the
involvement of ryanodine-sensitive intracellular Ca2+ stores in TNF-α mediated inhibition
of LTP.
| Item Type: |
Article
|
| Keywords: |
Tumor necrosis factor-α; Long-term potentiation; MCPG, MPEP; Group I mGluR; Ryanodine;
Intracellular calcium store; |
| Academic Unit: |
Faculty of Science and Engineering > Biology |
| Item ID: |
7192 |
| Identification Number: |
https://doi.org/10.1016/j.brainres.2006.12.019 |
| Depositing User: |
Professor Paul Moynagh
|
| Date Deposited: |
18 Jul 2016 09:10 |
| Journal or Publication Title: |
Brain Research |
| Publisher: |
Elsevier |
| Refereed: |
Yes |
| Funders: |
Higher Education Authority (HEA) |
| URI: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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