Glutaric aciduria type I: Pathomechanisms of neurodegeneration

In organotypic corticostriatal and hippocampal slice cultures from rat brai n, 3-hydroxyglutaric acid but not glutaric and glutaconic acids induced neu rodegeneration by activation of NMDA receptors. Electrophysiological invest igations (Xenopus laevis oocytes expressing glutamate receptors; rat mixed cortex culture) revealed no direct interaction of 3-hydroxyglutaric acid wi th glutamate receptors. We speculate that 3-hydroxyglutaric acid induces a mild energy deprivation that interferes with the voltage-dependent Mg2+-blo ck of NMDA receptors.