The effect of N-acetyl-aspartyl-glutamate and N-acetyl-aspartate on white matter oligodendrocytes
| Autor: | Anna Wade, Nicola B. Hamilton, Karolina Kolodziejczyk, Ragnhildur Thóra Káradóttir, David Attwell |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Patch-Clamp Techniques Canavan Disease Pelizaeus-Merzbacher Disease Pelizaeus-Merzbacher-like disease Action Potentials Glutamic Acid glutamate Biology Receptors N-Methyl-D-Aspartate Tissue Culture Techniques 03 medical and health sciences Myelin 0302 clinical medicine Cerebellum Internal medicine Canavan's disease medicine Animals Leucodystrophy Pelizaeus-Merzbacher-like disease Canavan's disease glutamate NMDA Receptor Evoked Potentials 030304 developmental biology Aspartic Acid 0303 health sciences Hydrolysis Glutamate receptor Dipeptides Original Articles Glutamic acid Oligodendrocyte Rats Oligodendroglia medicine.anatomical_structure Endocrinology NMDA nervous system Metabotropic glutamate receptor Neuroglia NMDA receptor Calcium Neurology (clinical) leucodystrophy 030217 neurology & neurosurgery |
| Zdroj: | Brain, 132 (6) pp. 1496-1508. (2009) Brain |
| ISSN: | 1460-2156 0006-8950 |
| DOI: | 10.1093/brain/awp087 |
| Popis: | Elevations of the levels of N-acetyl-aspartyl-glutamate (NAAG) and N-acetyl-aspartate (NAA) are associated with myelin loss in the leucodystrophies Canavan's disease and Pelizaeus-Merzbacher-like disease. NAAG and NAA can activate and antagonize neuronal N-methyl-D-aspartate (NMDA) receptors, and also act on group II metabotropic glutamate receptors. Oligodendrocytes and their precursors have recently been shown to express NMDA receptors, and activation of these receptors in ischaemia leads to the death of oligodendrocyte precursors and the loss of myelin. This raises the possibility that the failure to develop myelin, or demyelination, occurring in the leucodystrophies could reflect an action of NAAG or NAA on oligodendrocyte NMDA receptors. However, since the putative subunit composition of NMDA receptors on oligodendrocytes differs from that of neuronal NMDA receptors, the effects of NAAG and NAA on them are unknown. We show that NAAG, but not NAA, evokes an inward membrane current in cerebellar white matter oligodendrocytes, which is reduced by NMDA receptor block (but not by block of metabotropic glutamate receptors). The size of the current evoked by NAAG, relative to that evoked by NMDA, was much smaller in oligodendrocytes than in neurons, and NAAG induced a rise in [Ca(2+)](i) in neurons but not in oligodendrocytes. These differences in the effect of NAAG on oligodendrocytes and neurons may reflect the aforementioned difference in receptor subunit composition. In addition, as a major part of the response in oligodendrocytes was blocked by tetrodotoxin (TTX), much of the NAAG-evoked current in oligodendrocytes is a secondary consequence of activating neuronal NMDA receptors. Six hours exposure to 1 mM NAAG did not lead to the death of cells in the white matter. We conclude that an action of NAAG on oligodendrocyte NMDA receptors is unlikely to be a major contributor to white matter damage in the leucodystrophies. |
| Databáze: | OpenAIRE |
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