Evidence for a role for the group I metabotropic glutamate receptor in the inhibitory effect of tumor necrosis factor-α on long-term potentiation
| Autor: | Derval Cumiskey, Paul N. Moynagh, Marion P. Butler, John J. O'Connor |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
MAPK/ERK pathway
Male Time Factors Long-Term Potentiation Hippocampus Pharmacology Biology In Vitro Techniques Receptors Metabotropic Glutamate Models Biological Animals Drug Interactions Molecular Biology Ryanodine receptor Ryanodine Tumor Necrosis Factor-alpha General Neuroscience Dentate gyrus musculoskeletal neural and ocular physiology Antagonist Long-term potentiation Neural Inhibition Electric Stimulation Rats nervous system Metabotropic glutamate receptor Synaptic plasticity Dentate Gyrus Neurology (clinical) Neuroscience Excitatory Amino Acid Antagonists Developmental Biology |
| Popis: | 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)-alpha, 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-alpha have yet to be elucidated. This study investigated if metabotropic glutamate receptors (mGluRs) are functionally linked to the inhibitory effect of TNF-alpha on LTP in the rat dentate gyrus in vitro. We report that the impairment of early-LTP by TNF-alpha is significantly attenuated by prior application of the group I/II mGluR antagonist MCPG and more specifically the mGluR5 antagonist MPEP. Since TNF-alpha is now known to cause transient increases in intracellular Ca(2+) levels from ryanodine-sensitive stores, we explored the possibility that disruption of intracellular Ca(2+) homeostasis could be involved. Ryanodine was found to significantly reverse the inhibition of LTP by TNF-alpha. From these studies we propose that the TNF-alpha 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 Ca(2+) stores in TNF-alpha mediated inhibition of LTP. |
| Databáze: | OpenAIRE |
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