Reduced serotonin and 3-hydroxyanthranilic acid levels in serum of cystatin B-deficient mice, a model system for progressive myoclonus epilepsy.
OBJECTIVE
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 (5-HT) and KYN pathways were determined in serum of EPM1 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.
Arbatova
Jelena
J
Glenlab Niini Ltd., Helsinki, Finland.
D'Amato
Elena
E
Vaarmann
Annika
A
Zharkovsky
Alex
A
Reeben
Mati
M
D015095:3-Hydroxyanthranilic Acid / Q000032:analysis* / Q000378:metabolism; D000328:Adult; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D055313:Cystatin B; D015891:Cystatins / Q000172:deficiency* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007737:Kynurenine / Q000378:metabolism*; D008297:Male; D051379:Mice; D020191:Myoclonic Epilepsies, Progressive / Q000097:blood* / Q000378:metabolism; D012701:Serotonin / Q000097:blood*; D014364:Tryptophan / Q000378:metabolism*
C524994:CSTB protein, human; C524992:Cstb protein, mouse; D015891:Cystatins; D015095:3-Hydroxyanthranilic Acid; D012701:Serotonin; D007737:Kynurenine; D055313:Cystatin B; D014364:Tryptophan