TY - JOUR
T1 - Involvement of Na+, K+-ATPase and Endogenous Digitalis-Like Compounds in Depressive Disorders
AU - Goldstein, Inbal
AU - Levy, Talia
AU - Galili, Dana
AU - Ovadia, Haim
AU - Yirmiya, Raz
AU - Rosen, Haim
AU - Lichtstein, David
N1 - Funding Information:
This study was supported in part by The Wolfson Foundation for Scientific Research, The Hebrew University Jerusalem, Israel.
PY - 2006/9/1
Y1 - 2006/9/1
N2 - 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 3H-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: 3H-ouabain binding in bipolar patients was significantly lower than in major depressed and schizophrenic patients. Na+, K+-ATPase α 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.
AB - 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 3H-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: 3H-ouabain binding in bipolar patients was significantly lower than in major depressed and schizophrenic patients. Na+, K+-ATPase α 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.
KW - Digitalis-like compounds
KW - K-ATPase
KW - LPS
KW - Na
KW - forced swimming
KW - manic depression
KW - mood disorder
KW - ouabain
UR - http://www.scopus.com/inward/record.url?scp=33747886633&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2005.12.021
DO - 10.1016/j.biopsych.2005.12.021
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C2 - 16712803
AN - SCOPUS:33747886633
SN - 0006-3223
VL - 60
SP - 491
EP - 499
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 5
ER -