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Impaired glutamine metabolism in NMDA receptor hypofunction induced by MK801
Author(s) -
Brenner Eiliv,
Kondziella Daniel,
Håberg Asta,
Sonnewald Ursula
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03311.x
Subject(s) - glutamate receptor , nmda receptor , glutamine , medicine , chemistry , endocrinology , dizocilpine , ampa receptor , biochemistry , receptor , biology , amino acid
Paradoxically, glutamate receptor antagonists have neurotoxic and psychotogenic properties in addition to their neuroprotective potential during excessive glutamate release. In the present study the non‐competitive N ‐methyl‐ d ‐aspartate (NMDA) receptor antagonist MK801 was used to examine glial–neuronal interactions in NMDA receptor hypofunction. Rats were given a subanesthetic dose of MK801 together with [1‐ 13 C]glucose and [1,2‐ 13 C]acetate, and brains were removed 20 min later. Analyses of extracts from cingulate, retrosplenial plus middle frontal cortices (CRFC) and temporal lobe were performed using HPLC and 13 C and 1 H nuclear magnetic resonance spectroscopy. Hypofunction of the NMDA receptor induced similar changes in both brain areas investigated; however, the changes were most pronounced in the temporal lobe. Generally, only labeling from [1‐ 13 C]glucose was affected by MK801. In CRFC and temporal lobe amounts of both labeled and unlabeled glutamine were increased, whereas those of aspartate were decreased. In the CRFC the decrease in labeling of aspartate was greater than the decrease in concentration, leading to decreased 13 C enrichment. In temporal lobe, not in CRFC, increased concentrations of glutamate, GABA, succinate, glutathione and inositol were detected together with increased labeling of GABA and succinate from [1‐ 13 C]glucose. 13 C Enrichment was decreased in glutamate and increased in succinate. The results point towards a disturbance in glutamate–glutamine cycling and thus interaction between neurons and glia, since labeling of glutamate and glutamine from glucose was affected differently.