NMDA inhibitors cause apoptosis of pyramidal neurons in mature piriform cortex: evidence for a nitric oxide-mediated effect involving inhibitory interneurons
| Autor: | Lijun Zhou, Vassilis E. Koliatsos, David Chen, Annie M. Welsh |
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| Rok vydání: | 2006 |
| Předmět: |
Indazoles
Time Factors Excitotoxicity Apoptosis Nitric Oxide Synthase Type I Biology Paralimbic cortex medicine.disease_cause Inhibitory postsynaptic potential Nitric Oxide Models Biological Receptors N-Methyl-D-Aspartate Article Rats Sprague-Dawley Cellular and Molecular Neuroscience Microscopy Electron Transmission Interneurons Piriform cortex medicine Animals Drug Interactions Enzyme Inhibitors Pharmacology Cerebral Cortex Pyramidal Cells Glutamate receptor food and beverages Neural Inhibition Olfactory bulb Rats medicine.anatomical_structure nervous system Cerebral cortex Female Pyramidal cell Dizocilpine Maleate Neuroscience Excitatory Amino Acid Antagonists |
| Zdroj: | Neuropharmacology. 52(7) |
| ISSN: | 0028-3908 |
| Popis: | Pyramidal relay neurons in limbic cortex are vulnerable to denervation lesions, i.e. pyramidal neurons in layer IIalpha of piriform cortex undergo transsynaptic apoptosis after lesions that interrupt their inputs from the olfactory bulb. We have previously established the role of inhibitory interneurons in elaborating signals that lead to the apoptosis of projection neurons in these lesion models, i.e. the upregulation of neuronal NOS and release of nitric oxide. Thus, we have proposed that cortical interneurons play an essential role in transducing injury to degenerative effects for nearby pyramidal neurons. In the present study, we extend the previous findings to a toxic model of degeneration of pyramidal neurons in the adult paralimbic cortex, i.e. after exposure to the NMDA channel blocker MK801. Our findings indicate that treatment of adult rats with MK801 in doses previously found to cause alterations in pyramidal neurons of the retrosplenial cortex (5mg/kg) results in an active caspase 3 (+), ultrastructurally apoptotic type of cell death involving the same projection neurons of layer IIalpha that are also vulnerable to bulbotomy lesions. Interneurons of layer I are induced by MK801 treatment to higher levels of nNOS expression and the selective nNOS inhibitor BRNI ameliorates pyramidal cell apoptosis caused by MK801. Our results indicate that certain pyramidal neurons in piriform cortex are very sensitive to NMDA blockade as they are to disconnection from modality-specific afferents and that inhibitory interneurons play significant roles in mediating various types of pro-apoptotic insults to cortical projection neurons via nNOS/NO signaling. |
| Databáze: | OpenAIRE |
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