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Hypothalamic digoxin-mediated model for epileptogenesis

Published online by Cambridge University Press:  24 June 2014

Ravi Kumar Kurup  and
Parameswara Achutha Kurup
Ravi Kumar Kurup
Affiliation:
Department of Medicine, Medical College Hospital, Trivandrum
Parameswara Achutha Kurup*
Affiliation:
Metabolic Disorders Research Center, Trivandrum, Kerala, India
*
Gouri Sadan, T.C.4/1525, North of Cliff House, Kattu Road, Kowdiar P.O.,Trivandrum, Kerala, India, Tel: 0471-541607; Fax: 91-0471-550782; E-mail: [email protected]
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Abstract

Background/aims:

This study assessed the changes in the isoprenoid pathway and its metabolites in seizure disorder (ILAE classification – I generalized – idiopathic generalized epilepsy with age-related onset – epilepsy with generalized tonic clonic seizures on awakening) and the metabolic cascade produced by isoprenoid pathway dysregulation.

Methods:

The following parameters were assessed in seizure disorder: isoprenoid pathway metabolites, tyrosine and tryptophan catabolites, glycoconjugates metabolism and red blood cell (RBC) membrane composition.

Results:

There was elevation in plasma HMG-CoA reductase activity, serum digoxin and dolichol and a reduction in RBC membrane Na-K+ ATPase activity, serum magnesium and ubiquinone levels. Serum tryptophan, serotonin, strychnine, nicotine and quinolinic acid were elevated while tyrosine, dopamine, morphine and norepinephrine were decreased. The total serum glycosaminoglycans and glycosaminoglycan fractions (except dermatan sulfate), the activity of glycosaminoglycans (GAG) degrading enzymes and glycohydrolases, carbohydrate residues of glycoproteins and serum glycolipids were elevated. Total serum cholesterol, LDL cholesterol and free fatty acids were increased while HDL cholesterol and triglycerides were unaltered. The concentration of membrane hexose, fucose, cholesterol and phospholipids in the RBC membrane decreased significantly but the total RBC membrane GAG was unaltered.

Conclusions:

Epileptogenesis could be due to a dysfunctional isoprenoidal pathway and paroxysmal hypothalamic digoxin hypersecretion.

Keywords

digoxindolicholisoprenoidseizure disorderubiquinone
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 15 , Issue 3 , June 2003 , pp. 115 - 121
Copyright
Copyright © 2003 Blackwell Munksgaard

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