REDUCTION OF GLUTAMATE TRANSPORTER FUNCTION IN DENTATE GYRUS GLIAL CELLS BUT NOT IN CA1 GLIAL CELLS FROM EPILEPTIC HUMANS WITH TEMPORAL LOBE SCLEROSIS
Abstract number :
3.053
Submission category :
Year :
2002
Submission ID :
899
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Angelique Bordey, Doris Wang, Dennis D. Spencer. Department of Neurosurgery, Yale University School of Medicine, New Haven, CT
RATIONALE: Glutamate uptake is mediated by high affinity glutamate transporters (GluTs) present in both neurons and astrocytes. Glutamate uptake into astrocytes is the most important uptake system in the central nervous system that prevents glutamate build-up and resultant excitotoxicity. Although a defect of glial glutamate uptake has been suggested, little is known about the function of glial GluTs in epileptic human tissue.
METHODS: Human glial cells were studied using whole-cell patch-clamp recordings in acute hippocampal slices from surgical patients with intractable temporal lobe epilepsy (TLE). Data were obtained 4 cases of intractable temporal lobe epilepsy (TLE) with hippocampal sclerosis (mesio temporal sclerosis MTS), and 8 [dsquote]control[dsquote] cases composed of 2 TLE cases without neuronal loss and 6 cases of tumors associated with seizures. To measure glutamate uptake currents, 1 mM D-aspartate was pressure applied on recorded glial cells.
RESULTS: Puff of D-aspartate induced small inward currents that were significantly reduced by 300mM threo-beta-hydroxyaspartate (THA), a substrate agonist of glial glutamate transporters (GluT), in all the tested glial cells. This identifies D-aspartate-induced currents as glutamate transport currents. In addition, D-asparate-induced currents were voltage-dependent and strictly inwardly rectifying between -70 and +30mV. In control tissue CA1 and dentate gyrus glia express different levels of activity of GluTs based on their current amplitude (see Table). Because larger GluT currents are associated with a larger intracellular Na+ accumulation known to stimulate glycolysis and energy production in glia, CA1 and dentate gyrus glial cells may have some intrinsic difference in their handling of energy production in response to the neuronal demand. In MTS patients there is a significant decrease of the GluT current amplitude in dentate gyrus glia. In addition, in 9 of 18 cells tested, D-aspartate or THA did not induce any current.
CONCLUSIONS: These data strongly suggest that glutamate uptake into dentate gyrus glia in MTS patients is impaired. This would lead to a significant increase of extracellular glutamate levels and could also result in a reduction in energy production in glia in these regions.[table1]
[Supported by: NIH P01-NS39092-03]