In vitro effects of d-2-hydroxyglutaric acid on glutamate binding, uptake and release in cerebral cortex of rats

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• 作者：Junqueira ; D&eacute ; bora ; Brusque ; Ana M. ; Porciú ; ncula ; Lisiane O. ; Rotta ; Liane N. ; et. al.
• 关键词：d-2-hydroxyglutaric aciduria ; d-2-hydroxyglutaric acid ; Excitotoxicity ; Glutamate ; Neurotransmitter ; Glutamate release ; Glutamate uptake ; Synaptosome ; DHGA ; d-2-hydroxyglutaric aciduria ; DGA ; d-2-hydroxyglutaric acid ; MRI ; Magnetic Resonance Imaging ; ETP
• 刊名：Journal of the Neurological Sciences
• 出版年：2004
• 期刊代码：178_0022510x
• 类别：med
• 出版时间：February 15, 2004
• 卷：217
• 期：2
• 页码：189-194
• 文件大小：137 K

摘要

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.