Neuroprotective effects of the mGlu5R antagonist MPEP towards quinolinic acid‐induced striatal toxicity: involvement of pre‐ and post‐synaptic mechanisms and lack of direct NMDA blocking activity
| Autor: | Maria Anna De Berardinis, Antonella Pèzzola, Valeria Nazzicone, Rosaria Reggio, Luisa Minghetti, Rita Pepponi, Patrizia Popoli, Rosa Luisa Potenza, Maria Rosaria Domenici, Claudio Frank, Alberto Martire, Annita Pintor, Marino Massotti, Maria Teresa Tebano, Rosa Grieco |
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| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty N-Methylaspartate Pyridines Microdialysis Receptor Metabotropic Glutamate 5 Neurotoxins Excitotoxicity Glutamic Acid Biology Receptors Metabotropic Glutamate medicine.disease_cause Biochemistry Neuroprotection Cellular and Molecular Neuroscience chemistry.chemical_compound Internal medicine mental disorders medicine Animals Neurotoxin Rats Wistar Maze Learning Cells Cultured Neurons L-Lactate Dehydrogenase Metabotropic glutamate receptor 5 Body Weight Glutamate receptor Electroencephalography Quinolinic Acid Rats Neostriatum Neuroprotective Agents Endocrinology Metabotropic receptor chemistry NMDA receptor Calcium Neurotoxicity Syndromes Excitatory Amino Acid Antagonists Quinolinic acid |
| Zdroj: | Journal of Neurochemistry. 89:1479-1489 |
| ISSN: | 1471-4159 0022-3042 |
| Popis: | The aim of this work was to investigate the potential neuroprotective effects of the metabotropic glutamate receptor 5 (mGlu5R) antagonist 2-Methyl-6-(phenylethynyl)-pyridine (MPEP) towards quinolinic acid (QA)-induced striatal excitoxicity. Intrastriatal MPEP (5 nmol/0.5 micro L) significantly attenuated the body weight loss, the electroencephalographic alterations, the impairment in spatial memory and the striatal damage induced by bilateral striatal injection of QA (210 nmol/0.7 micro L). In a second set of experiments, we aimed to elucidate the mechanisms underlying the neuroprotective effects of MPEP. In microdialysis studies in naive rats MPEP (80-250 micro m through the dialysis probe) significantly reduced the increase in glutamate levels induced by 5 mm QA. In primary cultures of striatal neurons MPEP (50 micro m) reduced the toxicity induced by direct application of glutamate [measured as release of lactate dehydrogenase [LDH]). Finally, we found that 50 micro m MPEP was unable to directly block NMDA-induced effects (namely field potential reduction in corticostriatal slices, as well as LDH release and intracellular calcium increase in striatal neurons). We conclude that: (i) MPEP has neuroprotective effects towards QA-induced striatal excitotoxicity; (ii) both pre- and post-synaptic mechanisms are involved; (iii) the neuroprotective effects of MPEP do not appear to involve a direct blockade of NMDA receptors. |
| Databáze: | OpenAIRE |
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