Glutaric aciduria type I: pathomechanisms of neurodegeneration.
In organotypic corticostriatal and hippocampal slice cultures from rat brain, 3-hydroxyglutaric acid but not glutaric and glutaconic acids induced neurodegeneration by activation of NMDA receptors. Electrophysiological investigations (Xenopus laevis oocytes expressing glutamate receptors; rat mixed cortex culture) revealed no direct interaction of 3-hydroxyglutaric acid with glutamate receptors. We speculate that 3-hydroxyglutaric acid induces a mild energy deprivation that interferes with the voltage-dependent Mg(2+)-block of NMDA receptors.
Department of Pediatrics, University of Hamburg, Germany.
K
K
Ullrich
B
B
Flott-Rahmel
P
P
Schluff
U
U
Musshoff
A
A
Das
T
T
Lücke
R
R
Steinfeld
E
E
Christensen
C
C
Jakobs
A
A
Ludolph
A
A
Neu
R
R
Röper
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D046508:Culture Techniques; D005977:Glutarates / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
C108959:3-hydroxyglutaric acid; D005977:Glutarates; D016194:Receptors, N-Methyl-D-Aspartate; C035736:glutaric acid