Metabotropic glutamate receptor subtype 4 selectively modulates both glutamate and GABA transmission in the striatum: implications for Parkinson’s disease treatment

  title={Metabotropic glutamate receptor subtype 4 selectively modulates both glutamate and GABA transmission in the striatum: implications for Parkinson’s disease treatment},
  author={Dario Cuomo and Giuseppina Martella and Emanuela Barabino and P. Platania and Daniela Vita and Graziella Madeo and Chelliah Selvam and Cyril Goudet and Nadia Oueslati and Jean-Philippe Pin and Francine C. Acher and Antonio Pisani and Corinne Beurrier and Christophe Melon and Lydia Kerkerian-Le Goff and Paolo Gubellini},
  journal={Journal of Neurochemistry},
Alterations of striatal synaptic transmission have been associated with several motor disorders involving the basal ganglia, such as Parkinson’s disease. For this reason, we investigated the role of group‐III metabotropic glutamate (mGlu) receptors in regulating synaptic transmission in the striatum by electrophysiological recordings and by using our novel orthosteric agonist (3S)‐3‐[(3‐amino‐3‐carboxypropyl(hydroxy)phosphinyl)‐hydroxymethyl]‐5‐nitrothiophene (LSP1‐3081) and l‐2‐amino‐4… 
Glutamatergic Receptors in Parkinson’s Disease
In this chapter, recent progress in the research of GluRs is reviewed with special emphasis on the molecular diversity of the mGluR system and its implications in the physiopathology of PD.
Therapeutic potential of targeting group III metabotropic glutamate receptors in the treatment of Parkinson's disease
  • S. Duty
  • Biology
    British journal of pharmacology
  • 2010
Overwhelming evidence obtained from in vitro studies and animal models of PD supports group III mGlu receptors as potentially important drug targets for providing both symptom relief and neuroprotection in PD.
Author ' s personal copy Invited review Group III and subtype 4 metabotropic glutamate receptor agonists : Discovery and pathophysiological applications in Parkinson ’ s disease
The effects of newly-designed group-III orthosteric agonists on neuroprotection, neurorestoration and reduction of L-DOPA induced dyskinesia in animal models of PD are reviewed.
Metabolic, synaptic and behavioral impact of 5‐week chronic deep brain stimulation in hemiparkinsonian rats
Data show that chronic STN HFS efficiently counteracts metabolic and synaptic defects due to dopaminergic lesion in both the striatum and SNr, and suggests that the long‐term benefits of this treatment rely both on the maintenance of acute effects and on delayed actions on the basal ganglia network.
Metabotropic Glutamate Receptors and Parkinson’s Disease: Basic and Preclinical Neuroscience
Data is provided showing that drugs acting on mGlu receptors can alleviate PD motor symptoms and reduce levodopa-induced dyskinesia in animal models of PD and recent clinical trials that confirm these findings.
Activation of metabotropic glutamate 4 receptors decreases L-DOPA-induced dyskinesia in a mouse model of Parkinson's disease.
Results indicate that co-administration of LSP1-2111 may improve the efficacy of standard L-DOPA therapy by attenuating its liability for dyskinesia.


Targeting Group III Metabotropic Glutamate Receptors Produces Complex Behavioral Effects in Rodent Models of Parkinson's Disease
Results show that activation of group III mGluRs in the GP provides benefits in parkinsonian rats, presumably by modulating GABAergic neurotransmission, and support the use of subtype-selective group IIImGluR agonists as a potential antiparkinsonian strategy.
Chronic high‐frequency stimulation of the subthalamic nucleus and L‐DOPA treatment in experimental parkinsonism: effects on motor behaviour and striatal glutamate transmission
It is shown for the first time that dyskinesiogenic L‐DOPA treatment and chronic STN HFS with antiakinetic effects induce opposite plastic rearrangements in the striatum, providing further evidence that striatal glutamatergic hyperactivity is a pathophysiological correlate of akinesia rather than LID.
Group III Metabotropic Glutamate-Receptor-Mediated Modulation of Excitatory Transmission in Rodent Substantia Nigra Pars Compacta Dopamine Neurons
It is determined that mGLUR4 mediates the group III mGluR modulation of excitatory transmission in the rat SNc, and an apparent species difference is discovered suggesting that in mice, both mgluR4 and mGlamR8 modulate excitatories transmission inThe SNc.
Impaired Cerebellar Synaptic Plasticity and Motor Performance in Mice Lacking the mGluR4 Subtype of Metabotropic Glutamate Receptor
The results indicate that an important function of mGluR4 is to provide a presynaptic mechanism for maintaining synaptic efficacy during repetitive activation, and suggest that the presence ofmGLUR4 at the parallel fiber→Purkinje cell synapse is required for maintaining normal motor function.
Allosteric modulation of group III metabotropic glutamate receptor 4: A potential approach to Parkinson's disease treatment
Evidence for in vivo behavioral effects of an allosteric potentiator of mGluRs is reported and it is suggested that potentiation ofmGluR4 may be a useful therapeutic approach to the treatment of PD.
Experimental Parkinsonism Alters Endocannabinoid Degradation: Implications for Striatal Glutamatergic Transmission
In a rat model of Parkinson's disease induced by unilateral nigral lesion with 6-hydroxydopamine, the striatal levels of anandamide, but not that of the other endocannabinoid 2-arachidonoylglycerol, were increased, and inhibition of an andamide hydrolysis might represent a possible target to decrease the abnormal cortical glutamatergic drive in Parkinson’s disease.