Abstract
Neurological dysfunction is common in patients with d-2-hydroxyglutaric aciduria (DHGA). However, the mechanisms underlying the neuropathology
of this disorder are far from understood. In the present study, we investigated the
in vitro effects of d-2-hydroxyglutaric acid (DGA) at various concentrations (0.1–1.0 mM) on various parameters
of the glutamatergic system, namely the basal and potassium-induced release of l-[3H]glutamate by synaptosomal preparations, Na+-dependent l-[3H]glutamate uptake by synaptosomal preparations and Na+-independent l-[3H]glutamate uptake by synaptic vesicles, as well as of Na+-independent and dependent l-[3H]glutamate binding to synaptic plasma membranes from cerebral cortex of male adult
Wistar rats. We observed that DGA significantly increased synaptosomal l-[3H]glutamate uptake, without altering the other parameters. Although these findings
do not support a direct excitotoxic action for DGA since the metabolite did not affect
important parameters of the main neurotransmission system, they do not exclude a direct
action of DGA on NMDA or other glutamate receptors. More comprehensive studies are
therefore necessary to evaluate the exact role of DGA on neurotransmission.
Keywords
Abbreviations:
DHGA (d-2-hydroxyglutaric aciduria), DGA (d-2-hydroxyglutaric acid), MRI (Magnetic Resonance Imaging), ETP (electron transfer flavoprotein)To read this article in full you will need to make a payment
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Article info
Publication history
Accepted:
October 3,
2003
Received in revised form:
August 19,
2003
Received:
June 13,
2003
Identification
Copyright
© 2003 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
