A hypothalamic digoxin mediated model for conscious and subliminal perception
| Autor: | PA Kurup, A. Ravi Kumar |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Male medicine.medical_specialty Digoxin Consciousness ATPase Excitotoxicity Hypothalamus Models Psychological Subliminal Stimulation medicine.disease_cause chemistry.chemical_compound Dolichol Internal medicine Dolichols medicine Humans Enzyme Inhibitors Biological Psychiatry Tryptophan transport biology Middle Aged Psychiatry and Mental health Endocrinology Neurology chemistry biology.protein Schizophrenia NMDA receptor Female Hydroxymethylglutaryl CoA Reductases Neurology (clinical) Intracellular medicine.drug Quinolinic acid |
| Zdroj: | Journal of neural transmission (Vienna, Austria : 1996). 108(7) |
| ISSN: | 0300-9564 |
| Popis: | The isoprenoid pathway and its metabolites – digoxin, dolichol and ubiquinone were assessed in schizophrenia. There was an upregulation of the isoprenoid pathway as evidenced by elevated HMG CoA reductase activity. Digoxin, an endogenous Na+-K+ ATPase inhibitor secreted by the hypothalamus was found to be elevated and RBC membrane Na+-K+ ATPase activity was found to be reduced in schizophrenia. Membrane Na+-K+ ATPase inhibition can result in increased intracellular Ca2+ and reduced magnesium levels. Hypothalamic digoxin can modulate conscious and subliminal perception and its dysfunction may lead on to schizophrenia. Digoxin can also preferentially upregulate tryptophan transport over tyrosine resulting in increased levels of depolarising tryptophan catabolites – serotonin and quinolinic acid (NMDA agonist), and decreased levels of hyperpolarising tyrosine catabolites – dopamine and noradrenaline contributing to membrane Na+-K+ ATPase inhibition. NMDA excitotoxicity could result from hypomagnesemia induced by membrane Na+-K+ ATPase inhibition and quinolinic acid, an NMDA agonist acting on the NMDA receptor. Hypomagnesemia and increased dolichol level can affect glycoconjugate metabolism and membranogenesis leading on to disordered synaptic connectivity in the limbic allocortex and defective presentation of viral antigens and neuronal antigens contributing to autoimmunity and viral persistance important in the pathogenesis. Membrane Na+-K+ ATPase inhibition can produce immune activation, a component of autoimmunity. Mitochondrial dysfunction consequent to altered calcium/magnesium ratios and reduced ubiquinone levels can result in increased free radical generation and reduced free radical scavenging & defective apoptosis leading on to abnormal synaptogenesis. Schizophrenia can thus be considered as a syndrome of hypothalamic digoxin hypersecretion consequent to an upregulated isoprenoid pathway. |
| Databáze: | OpenAIRE |
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