Reduced serotonin and 3-hydroxyanthranilic acid levels in serum of cystatin B-deficient mice, a model system for progressive myoclonus epilepsy

Purpose: To evaluate the levels of tryptophan and its metabolites along serotonin (5-HT) and kynurenine (KYN) pathways in serum of progressive myoclonus epilepsy (EPM1) patients and cystatin B (CSTB)-deficient mice, a model system for EPM1. Methods: Tryptophan and its metabolites along serotonin (5HT) and KYN pathways were determined in serum of EPM I patients and CSTB-deficient mice by reverse-phase high-pressure liquid chromatography (HPLC) with electrochemical detection. Results: Reduced levels of 5-HT and KYN intermediate metabolite 3-hydroxyanthranilic acid were found in serum of CSTB-deficient mice. A similar trend was found in EPM1 patients. Although tryptophan concentration was reduced in serum of EPM1 patients, no such decrease was observed in CSTB-deficient mice. Conclusions: The present study demonstrates that tryptophan metabolism along 5-HT and KYN pathways are disrupted in EPM1 Further studies are needed to elucidate the role of KYN pathway in pathogenesis of EPM1.