title: Reduced astrocytic contribution to the turnover of glutamate, glutamine, and GABA characterizes the latent phase in the kainate model of temporal lobe epilepsy.
abstract: The occurrence of spontaneous seizures in mesial temporal lobe epilepsy (MTLE) is preceded by a latent phase that provides a time window for identifying and treating patients at risk. However, a reliable biomarker of epileptogenesis has not been established and the underlying processes remain unclear. Growing evidence suggests that astrocytes contribute to an imbalance between excitation and inhibition in epilepsy. Here, astrocytic and neuronal neurotransmitter metabolism was analyzed in the latent phase of the kainate model of MTLE in an attempt to identify epileptogenic processes and potential biomarkers. Fourteen days after status epilepticus, [1-(13)C]glucose and [1,2-(13)C]acetate were injected and the hippocampal formation, entorhinal/piriform cortex, and neocortex were analyzed by (1)H and (13)C magnetic resonance spectroscopy. The (13)C enrichment in glutamate, glutamine, and γ-aminobutyric acid (GABA) from [1-(13)C]glucose was decreased in all areas. Decreased GABA content was specific for the hippocampal formation, together with a pronounced decrease in astrocyte-derived [1,2-(13)C]GABA and a decreased transfer of glutamine for the synthesis of GABA. Accumulation of branched-chain amino acids combined with decreased [4,5-(13)C]glutamate in hippocampal formation could signify decreased transamination via branched-chain aminotransferase in astrocytes. The results point to astrocytes as major players in the epileptogenic process, and (13)C enrichment of glutamate and GABA as potential biomarkers.
authors.affiliation: Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Silje
authors.initials: S
authors.lastname: Alvestad
authors.forename: Janniche
authors.initials: J
authors.lastname: Hammer
authors.forename: Hong
authors.initials: H
authors.lastname: Qu
authors.forename: Asta
authors.initials: A
authors.lastname: Håberg
authors.forename: Ole Petter
authors.initials: OP
authors.lastname: Ottersen
authors.forename: Ursula
authors.initials: U
authors.lastname: Sonnewald
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D002247:Carbon Isotopes / Q000378:metabolism; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006624:Hippocampus; D007553:Isotope Labeling; D007608:Kainic Acid / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D000637:Transaminases; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000596:Amino Acids; D002247:Carbon Isotopes; D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000637:Transaminases; C019798:branched-chain-amino-acid transaminase; D007608:Kainic Acid