Moclobemide attenuates anoxia and glutamate-induced neuronal damage in vitro independently of interaction with glutamate receptor subtypes
| Autor: | François Xavier Bernard, Rémy Steinschneider, Marc Verleye, Jean-Marie Gillardin |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Monoamine Oxidase Inhibitors
Cell Survival medicine.drug_class Moclobemide Glutamic Acid AMPA receptor Pharmacology Biology Neuroprotection chemistry.chemical_compound medicine Animals Rats Wistar Hypoxia Neurotransmitter Molecular Biology Cells Cultured Cerebral Cortex Neurons Veratridine Monoamine oxidase inhibitor General Neuroscience Sodium Glutamate receptor Rats Neuroprotective Agents Receptors Glutamate chemistry Biochemistry Metabotropic glutamate receptor Astrocytes Potassium NMDA receptor Calcium Neurology (clinical) Developmental Biology |
| Zdroj: | Brain Research. 1138:30-38 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/j.brainres.2006.12.089 |
| Popis: | Recent data suggested the existence of a bidirectional relation between depression and neurodegenerative diseases resulting from cerebral ischemia injury. Glutamate, a major excitatory neurotransmitter, has long been recognised to play a key role in the pathophysiology of anoxia or ischemia, due to its excessive accumulation in the extracellular space and the subsequent activation of its receptors. A characteristic response to glutamate is the increase in cytosolic Na(+) and Ca(2+) levels which is due mainly to influx from the extracellular space, with a consequent cell swelling and oxidative metabolism dysfunction. The present study examined the in vitro effects of the antidepressant and type-A monoamine oxidase inhibitor, moclobemide, in neuronal-astroglial cultures from rat cerebral cortex exposed to anoxia (for 5 and 7 h) or to glutamate (2 mM for 6 h), two in vitro models of brain ischemia. In addition, the affinity of moclobemide for the different glutamate receptor subtypes and an interaction with the cell influx of Na(+) and of Ca(2+) enhanced by veratridine and K(+) excess, respectively, were evaluated. Moclobemide (10-100 microM) included in the culture medium during anoxia or with glutamate significantly increased in a concentration-dependent manner the amount of surviving neurons compared to controls. Moclobemide displayed no binding affinity for the different glutamate receptor subtypes (IC(50)>100 microM) and did not block up to 300 microM the entry of Na(+) and of Ca(2+) activated by veratridine and K(+), respectively. These results suggest that the neuroprotective properties of moclobemide imply neither the glutamate neurotransmission nor the Na(+) and Ca(2+) channels. |
| Databáze: | OpenAIRE |
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