Limbic structures show altered glial-neuronal metabolism in the chronic phase of kainate induced epilepsy.
A better understanding is needed of how glutamate metabolism is affected in mesial temporal lobe epilepsy (MTLE). Here we investigated glial-neuronal metabolism in the chronic phase of the kainate (KA) model of MTLE. Thirteen weeks following systemic KA, rats were injected i.p. with [1-(13)C]glucose. Brain extracts from hippocampal formation, entorhinal cortex, and neocortex, were analyzed by (13)C and (1)H magnetic resonance spectroscopy to quantify (13)C labeling and concentrations of metabolites, respectively. The amount and (13)C labeling of glutamate were reduced in the hippocampal formation and entorhinal cortex of epileptic rats. Together with the decreased concentration of NAA, these results indicate neuronal loss. Additionally, mitochondrial dysfunction was detected in surviving glutamatergic neurons in the hippocampal formation. In entorhinal cortex glutamine labeling and concentration were unchanged despite the reduced glutamate content and label, possibly due to decreased oxidative metabolism and conserved flux of glutamate through glutamine synthetase in astrocytes. This mechanism was not operative in the hippocampal formation, where glutamine labeling was decreased. In neocortex labeling and concentration of GABA were increased in epileptic rats, possibly representing a compensatory mechanism. The changes in the hippocampus might be of pathophysiological importance and merit further studies aiming at resolving metabolic causes and consequences of MTLE.
Alvestad
Silje
S
Department of Neuroscience, Norwegian University of Science and Technology (NTNU), MTFS, Trondheim 7489, Norway.
Hammer
Janniche
J
Eyjolfsson
Elvar
E
Qu
Hong
H
Ottersen
Ole Petter
OP
Sonnewald
Ursula
U
D000818:Animals; D002247:Carbon Isotopes; D002908:Chronic Disease; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism*; D007608:Kainic Acid / Q000633:toxicity*; D008032:Limbic System / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011522:Protons; D051381:Rats; D017207:Rats, Sprague-Dawley
D002247:Carbon Isotopes; D011522:Protons; D007608:Kainic Acid
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