Hypothalamic digoxin and hemispheric chemical dominance: relation to speech and language dysfunction.
The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. Since endogenous digoxin can regulate neurotransmitter transport and dolichols can modulate glycoconjugate synthesis important in synaptic connectivity, the pathway was assessed in patients with dyslexia, delayed recovery from global aphasia consequent to a dominant hemispheric thrombotic infarct, and developmental delay of speech milestone. The pathway was also studied in right hemispheric, left hemispheric, and bihemispheric dominance to find out the role of hemispheric dominance in the pathogenesis of speech disorders. The plasma/serum--activity of HMG CoA reductase, magnesium, digoxin, dolichol, ubiquinone--and tryptophan/tyrosine catabolic patterns, as well as RBC (Na+)-K+ ATPase activity, were measured in the above mentioned groups. The glycoconjugate metabolism and membrane composition was also studied. The study showed that in dyslexia, developmental delay of speech milestone, and delayed recovery from global aphasia there was an upregulated isoprenoidal pathway with increased digoxin and dolichol levels. The membrane (Na+)-K+ ATPase activity, serum magnesium and ubiquinone levels were low. The tryptophan catabolites were increased and the tyrosine catabolites including dopamine decreased in the serum contributing to a speech dysfunction. There was an increase in carbohydrate residues of glycoproteins, glycosaminoglycans, and glycolipids levels as well as an increased activity of GAG degrading enzymes and glyco hydrolases in the serum. The cholesterol:phospholipid ratio of RBC membrane increased and membrane glycoconjugates showed a decrease. All of these could contribute to altered synaptic inactivity in these disorders. The patterns correlated with those obtained in right hemispheric chemical dominance. Right hemispheric chemical dominance may play a role in the genesis of these disorders. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test.
Kurup
Ravi Kumar
RK
Department of Neurology, Medical College Hospital, Trivandrum, Kerala, India.
Kurup
Parameswara Achutha
PA
D000293:Adolescent; D000328:Adult; D001037:Aphasia / Q000503:physiopathology; D002648:Child; D004077:Digoxin / Q000097:blood*; D004286:Dolichols / Q000097:blood; D004292:Dominance, Cerebral / Q000502:physiology; D004410:Dyslexia / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000097:blood; D004910:Erythrocyte Membrane / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006025:Glycosaminoglycans / Q000097:blood; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000097:blood; D007031:Hypothalamus / Q000378:metabolism*; D008274:Magnesium / Q000097:blood; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D011106:Polyisoprenyl Phosphates / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013064:Speech Disorders / Q000503:physiopathology*; D014451:Ubiquinone / Q000097:blood
D004286:Dolichols; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D006025:Glycosaminoglycans; D018377:Neurotransmitter Agents; D011106:Polyisoprenyl Phosphates; D014451:Ubiquinone; D004077:Digoxin; D006903:Hydroxymethylglutaryl CoA Reductases; D000254:Sodium-Potassium-Exchanging ATPase; D008274:Magnesium