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Glutamate and gamma-aminobutyric acid content and release of synaptosomes from temporal lobe epilepsy patients.

Abstract：

:During surgical intervention in medically refractory temporal lobe epilepsy (TLE) patients, diagnosed with either mesial temporal lobe sclerosis (MTS)- or tumor (T)-associated TLE, biopsies were taken from the anterior temporal neocortex and the hippocampal region. Synaptosomes, isolated from these biopsies were used to study intrasynaptosomal Ca(2+) levels ([Ca(2+)](i)), and glutamate and gamma-aminobutyric acid (GABA) contents and release. All synaptosomal preparations demonstrated a basal [Ca(2+)](i) of about 200 nM, except neocortical synaptosomes from MTS-associated TLE patients (420 nM). K(+)-induced depolarization resulted in a robust increase of the basal [Ca(2+)](i) in all preparations. Neocortical synaptosomes from TLE patients contained 22.9 +/- 3.0 nmol glutamate and 4.6 +/- 0.5 nmol GABA per milligram synaptosomal protein, whereas rat cortical synaptosomes contained twice as much glutamate and four times as much GABA. Hippocampal synaptosomes from MTS-associated TLE patients, unlike those from T-associated TLE patients, contained about 70% less glutamate and 55% less GABA than neocortical synaptosomes. Expressed as percentage of total synaptosomal content, synaptosomes from MTS-associated TLE patients exhibited an increased basal and a reduced K(+)-induced glutamate and GABA release compared to rat cortical synaptosomes. In MTS-associated TLE patients, only GABA release from neocortical synaptosomes was partially Ca(2+)-dependent. Control experiments in rat synaptosomes demonstrated that at least part of the reduction in K(+)-induced release can be ascribed to resection-induced hypoxia in biopsies. Thus, synaptosomes from MTS-associated TLE patients exhibit a significant K(+)-induced increase in [Ca(2+)](i), but the consequent release of glutamate and GABA is severely impaired. Our data show that at least part of the differences in glutamate and GABA content and release between human biopsy material and fresh rat tissue is due to the resection time.

journal_name

J Neurosci Res

journal_title

Journal of neuroscience research

authors

Hoogland G,Hens JJ,De Wit M,van Veelen CW,van Huffelen AC,Gispen WH,de Graan PN

doi

10.1002/(SICI)1097-4547(20000601)60:5<686::AID-JNR

keywords:

subject

Has Abstract

pub_date

2000-06-01 00:00:00

pages

686-95

issue

eissn

0360-4012

issn

1097-4547

pii

10.1002/(SICI)1097-4547(20000601)60:5<686::AID-JNR

journal_volume

pub_type

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Glutamate and gamma-aminobutyric acid content and release of synaptosomes from temporal lobe epilepsy patients.