Endogenous cardiac steroids in animal models of mania

Hodes, Anastasia; Rosen, Haim; Deutsch, Joseph; Lifschytz, Tzuri; Einat, Haim; Lichtstein, David

doi:10.1111/bdi.12413

Cited by 26 publications

(34 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…OUA inhibits NKA at high doses, thereby inducing an abnormal increase in intracellular Ca +2 and Na + , which triggers apoptosis. High doses of OUA in the central nervous system (CNS) can be used to develop models of mania 20 , while OUA can afford protection at low doses, as evidenced in kidney studies 21, 22 .…”

Section: Introductionmentioning

confidence: 99%

Alpha 2 Na+,K+-ATPase silencing induces loss of inflammatory response and ouabain protection in glial cells

Kinoshita

Yshii

Orellana

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Ouabain (OUA) is a cardiac glycoside that binds to Na+,K+-ATPase (NKA), a conserved membrane protein that controls cell transmembrane ionic concentrations and requires ATP hydrolysis. At nM concentrations, OUA activates signaling pathways that are not related to its typical inhibitory effect on the NKA pump. Activation of these signaling pathways protects against some types of injury of the kidneys and central nervous system. There are 4 isoforms of the alpha subunit of NKA, which are differentially distributed across tissues and may have different physiological roles. Glial cells are important regulators of injury and inflammation in the brain and express the α1 and α2 NKA isoforms. This study investigated the role of α2 NKA in OUA modulation of the neuroinflammatory response induced by lipopolysaccharide (LPS) in mouse primary glial cell cultures. LPS treatment increased lactate dehydrogenase release, while OUA did not decrease cell viability and blocked LPS-induced NF-κB activation. Silencing α2 NKA prevented ERK and NF-κB activation by LPS. α2 NKA also regulates TNF-α and IL-1β levels. The data reported here indicate a significant role of α2 NKA in regulating central LPS effects, with implications in the associated neuroinflammatory processes.

show abstract

Section: Introductionmentioning

confidence: 99%

Alpha 2 Na+,K+-ATPase silencing induces loss of inflammatory response and ouabain protection in glial cells

Kinoshita

Yshii

Orellana

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The reduction in brain ECS by i.c.v. administration of anti-ouabain antibodies prevented the AMPH-induced hyperactivity and the increase in brain ECS levels [94]. …”

Section: Na+ K+-atpase and Ecs In Bdmentioning

confidence: 99%

“…Administration of amphetamine (AMPH), a potent central nervous system stimulant, to BALB/c and black Swiss mice, resulted in a marked increase in locomotor activity, accompanied by a threefold increase in brain ECS [94]. The reduction in brain ECS by i.c.v.…”

Section: Na+ K+-atpase and Ecs In Bdmentioning

confidence: 99%

“…We recently examined the effect of the CNS stimulant amphetamine (AMPH) and the reduction in brain ECS resulting from i.c.v. injection of specific anti-ouabain antibodies on behavior and ERK and Akt phosphorylation in the mouse frontal cortex [94]. The results showed a reduction in AMPH-induced hyperactivity [94], implicating the ECS in behavior.…”

Section: Na+ K+-atpase Signaling and Bdmentioning

confidence: 99%

“…injection of specific anti-ouabain antibodies on behavior and ERK and Akt phosphorylation in the mouse frontal cortex [94]. The results showed a reduction in AMPH-induced hyperactivity [94], implicating the ECS in behavior. Furthermore, we have shown that anti-ouabain antibody administration causes reduction in basal ERK phosphorylation in the mouse frontal cortex (Figure 1).…”

Section: Na+ K+-atpase Signaling and Bdmentioning

confidence: 99%

See 2 more Smart Citations

Na+, K+-ATPase Signaling and Bipolar Disorder

Lichtstein¹,

Ilani²,

Rosen³

et al. 2018

IJMS

Self Cite

View full text Add to dashboard Cite

Bipolar disorder (BD) is a severe and common chronic mental illness characterized by recurrent mood swings between depression and mania. The biological basis of the disease is poorly understood and its treatment is unsatisfactory. Although in past decades the “monoamine hypothesis” has dominated our understanding of both the pathophysiology of depressive disorders and the action of pharmacological treatments, recent studies focus on the involvement of additional neurotransmitters/neuromodulators systems and cellular processes in BD. Here, evidence for the participation of Na+, K+-ATPase and its endogenous regulators, the endogenous cardiac steroids (ECS), in the etiology of BD is reviewed. Proof for the involvement of brain Na+, K+-ATPase and ECS in behavior is summarized and it is hypothesized that ECS-Na+, K+-ATPase-induced activation of intracellular signaling participates in the mechanisms underlying BD. We propose that the activation of ERK, AKT, and NFκB, resulting from ECS-Na+, K+-ATPase interaction, modifies neuronal activity and neurotransmission which, in turn, participate in the regulation of behavior and BD. These observations suggest Na+, K+-ATPase-mediated signaling is a potential target for drug development for the treatment of BD.

show abstract

Reduction in endogenous cardiac steroids protects the brain from oxidative stress in a mouse model of mania induced by amphetamine

Hodes¹,

Lifschytz

Rosen³

et al. 2018

Brain Research Bulletin

View full text Add to dashboard Cite

Endogenous cardiac steroids in animal models of mania

Abstract: These results are in accordance with the notion that malfunctioning of the Na(+) , K(+) -ATPase/CS system may be involved in the manifestation of mania and identify this system as a potential new target for drug development.

Cited by 26 publications

References 55 publications

Alpha 2 Na+,K+-ATPase silencing induces loss of inflammatory response and ouabain protection in glial cells

Alpha 2 Na+,K+-ATPase silencing induces loss of inflammatory response and ouabain protection in glial cells

Na+, K+-ATPase Signaling and Bipolar Disorder

Reduction in endogenous cardiac steroids protects the brain from oxidative stress in a mouse model of mania induced by amphetamine

Contact Info

Product

Resources

About