Prolonged blockade of NMDA or mGluR5 glutamate receptors reduces nigrostriatal degeneration while inducing selective metabolic changes in the basal ganglia circuitry in a rodent model of Parkinson's disease
We compared the neuroprotective and metabolic effects of chronic treatment with ionotropic or metabotropic glutamate receptor antagonists, in rats bearing a unilateral nigrostriatal lesion induced by 6-hydroxydopamine (6-OHDA). The ionotropic, N-methyl-d-aspartate receptor antagonist MK-801 increase...
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doaj-77102f27e11c42f388edd0ebe4150f242021-03-20T04:52:05ZengElsevierNeurobiology of Disease1095-953X2006-04-0122119Prolonged blockade of NMDA or mGluR5 glutamate receptors reduces nigrostriatal degeneration while inducing selective metabolic changes in the basal ganglia circuitry in a rodent model of Parkinson's diseaseMarie-Thérèse Armentero0Roberto Fancellu1Giuseppe Nappi2Placido Bramanti3Fabio Blandini4Laboratory of Functional Neurochemistry, IRCCS Neurological Institute “C. Mondino”, Via Mondino, 2, 27100 Pavia, ItalyLaboratory of Functional Neurochemistry, IRCCS Neurological Institute “C. Mondino”, Via Mondino, 2, 27100 Pavia, Italy; University of Insubria, Varese, ItalyLaboratory of Functional Neurochemistry, IRCCS Neurological Institute “C. Mondino”, Via Mondino, 2, 27100 Pavia, Italy; Department of Neurology and Otorhinolaryngology, University of Rome “La Sapienza”, Rome, ItalyCentro Studi Neurolesi, University of Messina, ItalyLaboratory of Functional Neurochemistry, IRCCS Neurological Institute “C. Mondino”, Via Mondino, 2, 27100 Pavia, Italy; Corresponding author. Fax: +39 0382 380448.We compared the neuroprotective and metabolic effects of chronic treatment with ionotropic or metabotropic glutamate receptor antagonists, in rats bearing a unilateral nigrostriatal lesion induced by 6-hydroxydopamine (6-OHDA). The ionotropic, N-methyl-d-aspartate receptor antagonist MK-801 increased cell survival in the substantia nigra pars compacta (SNc) and corrected the metabolic hyperactivity (increased cytochrome oxidase activity) of the ipsilateral substantia nigra pars reticulata (SNr) associated with the lesion, but showed no effects on the 6-OHDA-induced hyperactivity of the subthalamic nucleus (STN). Significant—although less pronounced—protection of SNc neurons was also observed following treatment with the metabotropic glutamate receptor (mGluR5) antagonist 2-methyl-6-(phenylehtynyl)-pyridine (MPEP). As opposed to MK-801, MPEP abolished the STN metabolic hyperactivity associated with the nigrostriatal lesion, without affecting SNr activity. Specific modulation of STN hyperactivity obtained with mGluR5 blockade may, therefore, open interesting perspectives for the use of this class of compounds in the treatment of Parkinson's disease.http://www.sciencedirect.com/science/article/pii/S09699961050026646-HydroxydopamineBasal gangliaNeuroprotectionTyrosine hydroxylaseCytochrome oxidaseIonotropic |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marie-Thérèse Armentero Roberto Fancellu Giuseppe Nappi Placido Bramanti Fabio Blandini |
spellingShingle |
Marie-Thérèse Armentero Roberto Fancellu Giuseppe Nappi Placido Bramanti Fabio Blandini Prolonged blockade of NMDA or mGluR5 glutamate receptors reduces nigrostriatal degeneration while inducing selective metabolic changes in the basal ganglia circuitry in a rodent model of Parkinson's disease Neurobiology of Disease 6-Hydroxydopamine Basal ganglia Neuroprotection Tyrosine hydroxylase Cytochrome oxidase Ionotropic |
author_facet |
Marie-Thérèse Armentero Roberto Fancellu Giuseppe Nappi Placido Bramanti Fabio Blandini |
author_sort |
Marie-Thérèse Armentero |
title |
Prolonged blockade of NMDA or mGluR5 glutamate receptors reduces nigrostriatal degeneration while inducing selective metabolic changes in the basal ganglia circuitry in a rodent model of Parkinson's disease |
title_short |
Prolonged blockade of NMDA or mGluR5 glutamate receptors reduces nigrostriatal degeneration while inducing selective metabolic changes in the basal ganglia circuitry in a rodent model of Parkinson's disease |
title_full |
Prolonged blockade of NMDA or mGluR5 glutamate receptors reduces nigrostriatal degeneration while inducing selective metabolic changes in the basal ganglia circuitry in a rodent model of Parkinson's disease |
title_fullStr |
Prolonged blockade of NMDA or mGluR5 glutamate receptors reduces nigrostriatal degeneration while inducing selective metabolic changes in the basal ganglia circuitry in a rodent model of Parkinson's disease |
title_full_unstemmed |
Prolonged blockade of NMDA or mGluR5 glutamate receptors reduces nigrostriatal degeneration while inducing selective metabolic changes in the basal ganglia circuitry in a rodent model of Parkinson's disease |
title_sort |
prolonged blockade of nmda or mglur5 glutamate receptors reduces nigrostriatal degeneration while inducing selective metabolic changes in the basal ganglia circuitry in a rodent model of parkinson's disease |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2006-04-01 |
description |
We compared the neuroprotective and metabolic effects of chronic treatment with ionotropic or metabotropic glutamate receptor antagonists, in rats bearing a unilateral nigrostriatal lesion induced by 6-hydroxydopamine (6-OHDA). The ionotropic, N-methyl-d-aspartate receptor antagonist MK-801 increased cell survival in the substantia nigra pars compacta (SNc) and corrected the metabolic hyperactivity (increased cytochrome oxidase activity) of the ipsilateral substantia nigra pars reticulata (SNr) associated with the lesion, but showed no effects on the 6-OHDA-induced hyperactivity of the subthalamic nucleus (STN). Significant—although less pronounced—protection of SNc neurons was also observed following treatment with the metabotropic glutamate receptor (mGluR5) antagonist 2-methyl-6-(phenylehtynyl)-pyridine (MPEP). As opposed to MK-801, MPEP abolished the STN metabolic hyperactivity associated with the nigrostriatal lesion, without affecting SNr activity. Specific modulation of STN hyperactivity obtained with mGluR5 blockade may, therefore, open interesting perspectives for the use of this class of compounds in the treatment of Parkinson's disease. |
topic |
6-Hydroxydopamine Basal ganglia Neuroprotection Tyrosine hydroxylase Cytochrome oxidase Ionotropic |
url |
http://www.sciencedirect.com/science/article/pii/S0969996105002664 |
work_keys_str_mv |
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