Subscribe to RSS
DOI: 10.1055/s-0039-1694898
Role of Pyridoxal Phosphate in Modulation of Endogenous Kynurenic Acid Synthesis Associated with Hippocampal Sclerosis
Subject Editor:
Publication History
Publication Date:
31 July 2019 (online)
Objective: Hippocampal sclerosis (HS) is the most common form of drug-resistant epilepsy where temporal lobe structures are responsible for unprovoked seizures. The hallmark of HS is enhanced glutamatergic excitatory neurotransmission. Pyridoxal 5-phosphate (pLP) is an active form of vitamin B6 and plays an important role as a cofactor of various enzymes including kynurenine aminotransferase II (KAT II), which catalyzes kynurenic acid (KYNA) synthesis from kynurenine within cortical astrocytes. KYNA, a tryptophan metabolite, is the only natural inhibitor of glutamate receptors. The present study was designed to test the hypothesis that in HS, altered PLP concentration is responsible for reduced endogenous kynurenic acid synthesis in hippocampus.
Methods: Hippocampus from HS patients (n = 33) were used for this study. Tissues resected from tumor margin during brain tumor surgery of seizure-free patients as nonepileptic control (n = 14) were used. To determine total KYNA and PLP concentration, tissues were kept in perchloric acid at —80°C. Tissues were homogenized, centrifuged, and supernatants were collected and estimated using HPLC with fluorescence detection (pLP excitation 300 nm, emission 400 nm; KYNA excitation 344 nm, and emission 404 nm).
Results: KYNA concentration was significantly less in HS hippocampus (0.0244 ± 0.0219 ng/mg of protein) compared with nonepileptic controls (0.2117 ± 0.1332 ng/mg of protein). PLP concentration was also significantly less in HS patients (1.77 ± 3.96 mg/mg of protein) compared with controls (10.91 ± 11.34 ng/mg of protein).
Conclusion: PLP concentration is reduced which, we suspect, may consequences in decreased KYNA due to dysfunctional machinery to synthesize kynurenic acid from kynurenine in HS patients.