Involvement of Na(+), K(+)-ATPase and endogenous digitalis-like compounds in depressive disorders.
BACKGROUND
Sodium and potassium-activated adenosine triphosphatase (Na(+), K(+)-ATPase) and endogenous digitalis-like compounds (DLC) in the brain have been implicated in the pathogenesis of mood disorders. This hypothesis was examined by the determination of Na(+), K(+)-ATPase/DLC system in parietal cortex of patients with different mood disorders and two animal models of depression.


METHODS
Na(+), K(+)-ATPase concentrations in human brain synaptosomal fractions, from patients with mood disorders, schizophrenia, and normal individuals, were determined by (3)H-ouabain binding assay. Alpha isoforms were quantified by Western blotting. Brain DLC were measured using sensitive enzyme linked immunosorbant assay (ELISA). The effects of ouabain and ouabain-antibodies on behavior were determined in two animal models of depression.


RESULTS
(3)H-ouabain binding in bipolar patients was significantly lower than in major depressed and schizophrenic patients. Na(+), K(+)-ATPase alpha isoforms in synaptosomal fractions were not different among the groups. DLC levels in the parietal cortex of bipolar patients were significantly higher than in normal individuals and depressed patients. Injection of lipopolysaccharide (intraperitoneally) to rats elicited depression-like symptoms, which were significantly attenuated by pre-injection of ouabain-antibodies. Injection of ouabain and ouabain-antibodies (intracerebroventricular) reduced depression-like symptoms in the forced swimming test in rats.


CONCLUSIONS
The results support the possibility that Na(+), K(+)-ATPase and endogenous DLC participate in the pathogenesis of depressive disorders.
Goldstein
Inbal
I
Department of Physiology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Levy
Talia
T
Galili
Dana
D
Ovadia
Haim
H
Yirmiya
Raz
R
Rosen
Haim
H
Lichtstein
David
D
D000328:Adult; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001714:Bipolar Disorder / Q000201:enzymology; D002018:Bufanolides / Q000378:metabolism*; D002298:Cardenolides / Q000378:metabolism*; D003866:Depressive Disorder / Q000201:enzymology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000201:enzymology; D010042:Ouabain / Q000378:metabolism; D010296:Parietal Lobe / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012016:Reference Values; D012559:Schizophrenia / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013574:Synaptosomes / Q000201:enzymology*
D002018:Bufanolides; D002298:Cardenolides; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase