Metabolism is normal in astrocytes in chronically epileptic rats: a (13)C NMR study of neuronal-glial interactions in a model of temporal lobe epilepsy.
The aim of the present work was to study potential disturbances in metabolism and interactions between neurons and glia in the lithium-pilocarpine model of temporal lobe epilepsy. Rats chronically epileptic for 1 month received [1-(13)C]glucose, a substrate for neurons and astrocytes, and [1,2-(13)C]acetate, a substrate for astrocytes only. Analyses of extracts from cerebral cortex, cerebellum, and hippocampal formation (hippocampus, amygdala, entorhinal, and piriform cortices) were performed using (13)C and (1)H nuclear magnetic resonance spectroscopy and HPLC. In the hippocampal formation of epileptic rats, levels of glutamate, aspartate, N-acetyl aspartate, adenosine triphosphate plus adenosine diphosphate and glutathione were decreased. In all regions studied, labeling from [1,2-(13)C]acetate was similar in control and epileptic rats, indicating normal astrocytic metabolism. However, labeling of glutamate, GABA, aspartate, and alanine from [1-(13)C]glucose was decreased in all areas possibly reflecting neuronal loss. The labeling of glutamine from [1-(13)C]glucose was decreased in cerebral cortex and cerebellum and unchanged in hippocampal formation. In conclusion, no changes were detected in glial-neuronal interactions in the hippocampal formation while in cortex and cerebellum the flow of glutamate to astrocytes was decreased, indicating a disturbed glutamate-glutamine cycle. This is, to our knowledge, the first study showing that metabolic disturbances are confined to neurons inside the epileptic circuit.
Melø
Torun M
TM
Department of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Nehlig
Astrid
A
Sonnewald
Ursula
U
D000085:Acetates / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001923:Brain Chemistry; D002247:Carbon Isotopes; D002450:Cell Communication; D002908:Chronic Disease; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D009457:Neuroglia / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000085:Acetates; D002247:Carbon Isotopes; D018698:Glutamic Acid; D005947:Glucose