Neuronal and glial mGluR5 modulation prevents stretch-induced enhancement of NMDA receptor current

@article{Lea2002NeuronalAG,
  title={Neuronal and glial mGluR5 modulation prevents stretch-induced enhancement of NMDA receptor current},
  author={Paul M Lea and Stephanie J Custer and Stefano Vicini and Alan I. Faden},
  journal={Pharmacology Biochemistry and Behavior},
  year={2002},
  volume={73},
  pages={287-298}
}
Neuronal stretching in culture has been used to model diffuse axonal injury caused by head trauma, and activation of N-methyl-D-aspartate receptors (NMDARs) has been implicated in the pathophysiology of such injury. Here we report the effects of modulating injury severity and the metabotropic glutamate receptor subtype 5 (mGluR5) on NMDAR activity after stretch injury. Following mild stretch, cortical neurons plated upon a confluent layer of astrocytes (NG) exhibited both increased maximal… Expand
Modulation of stretch-induced enhancement of neuronal NMDA receptor current by mGluR1 depends upon presence of glia.
TLDR
The presence of glia significantly alters the nature of mGluR1-mediated modulation of NMDAR activity and stretch-induced injury, and indicates a significant neuronal/glial interaction between glial mGLUR1 and neuronal NMDA receptor activity. Expand
Excitatory synaptic transmission and network activity are depressed following mechanical injury in cortical neurons.
TLDR
The overriding effect of mechanical injury was long-term depression of excitatory neurotransmission that would be expected to contribute to the cognitive deficits of TBI. Expand
The role of NMDA and mGluR5 receptors in calcium mobilization and neurotoxicity of homocysteine in trigeminal and cortical neurons and glial cells
TLDR
G glutamatergic mechanisms of HCY‐induced sensitization and apoptosis of trigeminal nociceptors are suggested, which suggest elevation of intracellular Ca2+ by HCY in neurons is mediated by NMDA and mGluR5 receptors while SGC are activated through the mGLUR5 subtype. Expand
Activation of mGluR5 and inhibition of NADPH oxidase improves functional recovery after traumatic brain injury.
TLDR
The data suggest that the neuroprotective effects of activating mGluR5 receptors after TBI are mediated, in part, via the inhibition of NADPH oxidase. Expand
A multilayer network model of neuron-astrocyte populations in vitro reveals mGluR5 inhibition is protective following traumatic injury
TLDR
A multilayer network model of neuron-astrocyte connectivity was constructed, which captured distinct topology and response behavior from single cell type networks, and the effect of glutamatergic inhibition and mechanical injury on network topology was evaluated. Expand
Expression and cell distribution of metabotropic glutamate receptor 5 in the rat cortex following traumatic brain injury
TLDR
It is found that the protein level of mGluR5 was up-regulated by traumatic brain injury, while TBI-induced mGLUR5 mRNA expression displayed biphasic changes with up-regulation in the early time and down- regulation in the late time after TBI. Expand
Metabotropic glutamate receptor subtype 5 antagonists MPEP and MTEP.
TLDR
In vivo and in vitro characterization of the newer mGluR5 antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) indicates that it is more highly selective for mGLUR5 over mGlamR1, has no effect on other mGLuR subtypes, and has fewer off-target effects than MPEP. Expand
Antidepressant-like effect of the mGluR5 antagonist MTEP in an astroglial degeneration model of depression
TLDR
The obtained results indicate that the degeneration of astrocytes in the PFC by l-AAA may be a useful animal model of depression and suggest antidepressant potential of MTEP. Expand
Neuroprotective activity of the mGluR5 antagonists MPEP and MTEP against acute excitotoxicity differs and does not reflect actions at mGluR5 receptors
TLDR
Combined studies support the conclusion that MTEP has greater mGluR5 selectivity than MPEP, and that neuroprotection provided by either antagonist in neuronal cultures does not reflect inhibition of mGLUR5 receptors. Expand
Bursting of prefrontal cortex neurons in awake rats is regulated by metabotropic glutamate 5 (mGlu5) receptors: rate-dependent influence and interaction with NMDA receptors.
TLDR
Findings demonstrate that in awake animals mGlu5 receptors regulate the function of PFC neurons by two related mechanisms: rate-dependent excitatory influence on spontaneous burst activity; and potentiation of NMDA receptor mediated effects on firing rate and burst activity. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 70 REFERENCES
Activation of Metabotropic Glutamate Receptor Subtype mGluR1 Contributes to Post-Traumatic Neuronal Injury
TLDR
It is suggested that activation of mGLUR1 contributes to post-traumatic neuronal injury and that mGluR1 antagonists may have therapeutic potential in brain injury. Expand
Enhancement of AMPA-Mediated Current after Traumatic Injury in Cortical Neurons
TLDR
The difference in current densities between control and injured neurons was abolished when AMPA receptors desensitization was inhibited by the coapplication of AMPA and cyclothiazide or by the use of kainate as an agonist, suggesting that mechanical injury alters AMPA receptor desensITization. Expand
Reduction of Voltage-Dependent Mg2+ Blockade of NMDA Current in Mechanically Injured Neurons
TLDR
Stretch-induced injury was found to reduce the Mg2+ blockade, resulting in significantly larger ionic currents and increases in intracellular free calcium (Ca2+) concentration after NMDA stimulation of injured neurons. Expand
Selective Blockade of the mGluR1 Receptor Reduces Traumatic Neuronal Injury in Vitro and Improves Outcome after Brain Trauma
TLDR
Modulation of mGluR1 activity may have substantial therapeutic potential in brain injury, as demonstrated by inhibition of agonist induced phosphoinositide hydrolysis in in vitro system. Expand
An activity‐dependent switch from facilitation to inhibition in the control of excitotoxicity by group I metabotropic glutamate receptors
TLDR
It is concluded that group I mGlu receptors are subjected to an activity‐dependent switch in regulating excitotoxic neuronal death and, therefore, the recent ‘history’ of these receptors is critical for the response to agonists or antagonists. Expand
Inhibition of the electrogenic Na pump underlies delayed depolarization of cortical neurons after mechanical injury or glutamate.
TLDR
It is reported that SIDD is mediated by Na pump inhibition and is likely to result from reduced energy levels since the RMP of neurons dialyzed with a pipette solution containing 5 mM ATP were identical to controls. Expand
Activation of group I metabotropic glutamate receptors reduces neuronal apoptosis but increases necrotic cell death in vitro
TLDR
It is suggested that activation of mGluR1 exacerbates neuronal necrosis whereas both mGlamR1 and mGLUR5 play a role in attenuation of neuronal apoptosis, which is opposite of the effects on necrotic and apoptotic neuronal cell death. Expand
Potentiation of NMDA and AMPA responses by the specific mGluR5 agonist CHPG in spinal cord motoneurons
TLDR
The results suggest that both mGluR5 and mGLUR1 may act to enhance ionotropic glutamate responses but the two types ofmGluRs may have different intracellular mechanisms of action. Expand
Activation of Metabotropic Glutamate Receptor 5 Has Direct Excitatory Effects and Potentiates NMDA Receptor Currents in Neurons of the Subthalamic Nucleus
TLDR
It is reported that activation of group I metabotropic glutamate receptors (mGluRs) induces a direct excitation of STN neurons that is characterized by depolarization, increased firing frequency, and increased burst-firing activity, and the results suggest that mGluR5 may play an important role in the net excitatory drive to the STN from glutamatergic afferents. Expand
mGluR modulation of post‐traumatic neuronal death: role of NMDA receptors
TLDR
Study of the potential interaction between group I metabotropic glutamate receptors (mGluR) and NMDA receptors in mediating of post-traumatic neuronal death was studied using an in vitro trauma model, and findings are consistent with the conclusion that the effects of group I mGLUR activation on post- traumatic cell death are mediated only in part through NMDA receptor modulation. Expand
...
1
2
3
4
5
...