Effect of ouabain on sodium pump alpha-isoform expression in an animal model of mania

Hamid, Humera; Gao, Yonglin; Lei, Zhenmin; Hougland, M. Tyler; El‐Mallakh, Rif S.

doi:10.1016/j.pnpbp.2009.06.002

Cited by 16 publications

(13 citation statements)

References 31 publications

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“…It has been proposed that the ICV administration of ouabain in rats induces the neuronal ATPase hypoactivity, which is proposed to occur in mania and depression in humans. Previous studies showed that the ICV injection of ouabain induces hyperlocomotion (manic-like behavior), which persist for seven days a er a single injection 25,27 , suggesting that inhibition of brain Na/K ATPase activity causes hyperactivity. We also demonstrated that when evaluated immediately, 3h, 24h or seven days a er ICV injection, the ouabain administration increased rat spontaneous locomotion.…”

Section: Discussionmentioning

confidence: 99%

Decreased BDNF levels in amygdala and hippocampus after intracerebroventricular administration of ouabain

Jornada

Valvassori

Resende

et al. 2012

Rev. psiquiatr. clín.

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Objective: e present study aims to investigate the e ects of ouabain intracerebroventricular injection on BDNF levels in the amygdala and hippocampus of Wistar rats. Methods: Animals received a single intracerebroventricular injection of ouabain (10 -3 and 10 -2 M) or arti cial cerebrospinal uid and immediately, 1h, 24h, or seven days a er injection, BDNF levels were measured in the rat's amygdala and hippocampus by sandwich-ELISA (n = 8 animals per group). Results: When evaluated immediately, 3h, or 24h a er injection, ouabain in doses of 10 -2 and 10 -3 M does not alter BDNF levels in the amygdala and hippocampus. However, when evaluated seven days a er injection, ouabain in 10 -2 and 10 -3 M, showed a signi cant reduction in BDNF levels in both brain regions evaluated. Discussion: In conclusion, we propose that the ouabain decreased BDNF levels in the hippocampus and amygdala when assessed seven days a er administration, supporting the Na/K ATPase hypothesis for bipolar illness. ResumoObjetivo: O presente estudo tem como objetivo investigar os efeitos da injeção intracerebroventricular de ouabaína sobre os níveis de BDNF na amígdala e no hipocampo de ratos Wistar. Métodos: Os animais receberam uma única injeção intracerebroventricular de ouabaína (10 -3 and 10 -2 M) ou uido cerebroespinhal arti cial e, imediatamente, 3h, 24h ou sete dias após a injeção, os níveis de BDNF foram mensurados na amígdala e hipocampo dos ratos por ELISA sandwich (n = 8 animais por grupo). Resultados: Quando avaliados imediatamente após a injeção, 3h ou 24h, ouabaína nas doses 10 -2 e 10 -3 M não alterou os níveis de BDNF em ambas as estruturas avaliadas. Entretanto, quando avaliados sete dias após a injeção, ouabaína nas doses 10 -2 e 10 -3 M mostrou uma signi cante redução nos níveis de BDNF em amígdala e hipocampo. Conclusão: Em conclusão, propõe-se que a administração de ouabaína diminuiu os níveis de BDNF em amígdala e hipocampo quando avaliados sete dias após a injeção, suportando a hipótese da participação da Na/K ATPase no transtorno bipolar. Jornada LK, et al. / Rev Psiq Clín. 2012;39(5):157-60 Palavras-chave: BDNF, mania, Na/K ATPase, ouabaína.

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Section: Discussionmentioning

confidence: 99%

Decreased BDNF levels in amygdala and hippocampus after intracerebroventricular administration of ouabain

Jornada

Valvassori

Resende

et al. 2012

Rev. psiquiatr. clín.

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“…Na + /K + ‐ATPase inhibition by ouabain is known to decrease norepinephrine, dopamine, and serotonin uptake, and increase acetylcholine release (Moseley et al, 2007). Hamid et al (2009), showed that brain areas that upregulated sodium pump isoforms (frontal cortex and basal ganglia) maintained normal pump activity, while the hippocampus did not upregulate any isoforms, and experienced a decrease in pump activity. The alpha 3 isoform is neuron‐specific.…”

Section: Discussionmentioning

confidence: 99%

Effect of repeated restraint stress and clomipramine on Na⁺/K⁺‐ATPase activity and behavior in rats

Balk

Silva²,

Bridi³

et al. 2011

Intl J of Devlp Neuroscience

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Activation of the limbic-hypothalamic-pituitary-adrenal axis (LHPA) and the release of glucocorticoids are fundamental for the adaptive response and immediate survival of an organism in reaction to acute stimuli. However, high levels of glucocorticoids in the brain may produce neuronal injury and a decrease of Na(+)/K(+)-ATPase activity, with effects on neurotransmitter signaling, neural activity, as well as the whole animal behavior. Clomipramine is a tricyclic antidepressant that inhibits the reuptake of serotonin and norepinephrine by indirect actions on the dopaminergic system and LHPA axis. Its chronic use increases the body's ability to cope with stress; however, high doses can potentiate its side effects on memory, learning, and sensory motor function. The purpose of the present study was to compare the effect of repeated restraint stress and clomipramine treatment on Na(+)/K(+)-ATPase activity and on the behavior of male rats. Changes in the behavioral response were evaluated by measuring the memory, learning, anxiety, and exploratory responses. Our results showed that exposure to repeated restraint stress reduced levels of Na(+)/K(+)-ATPase in brain structures and changed short and long-term memory, learning, and exploratory response when compared to the control group. Exposure to clomipramine treatment increased anxiety levels and reduced Na(+)/K(+)-ATPase activity in the cerebral cortex as well as short term memory, learning, and exploratory response. In conclusion, the present results provide additional evidence concerning how repeated restraint stress and clomipramine chronically administered at higher dose levels affect the neural activity and behavior of male rats.

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“…, K ? -ATPase alpha 3 subunit mRNA in a few brain regions, mainly in the amygdala [78], and this isoform has been reported to be altered in animal models related to changes in behavior [79,80]. On the other hand, other subunits of this enzyme are present in the brain [81][82][83] and may be involved in the reduction observed in enzyme activity.…”

Section: Discussionmentioning

confidence: 99%

Na+, K+ ATPase Activity Is Reduced in Amygdala of Rats with Chronic Stress-Induced Anxiety-Like Behavior

et al. 2010

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In this study, we examined the effects of two chronic stress regimens upon anxiety-like behavior, Na(+), K(+)-ATPase activity and immunocontent, and oxidative stress parameters (antioxidant enzymes and reactive oxygen species production) in the amygdala. Male rats were subjected to chronic unpredictable and to chronic restraint stress for 40 days. Subsequently, anxiety-like behavior was examined. Both stressed groups presented increased anxiety-like behavior. Reduced amygdalal Na(+), K(+)-ATPase activity in the synaptic plasma membranes was also observed, without alterations in the amygdala immunocontent. In addition, when analyzing oxidative stress parameters, only superoxide dismutase activity was decreased in the amygdala of animals subjected to unpredictable stress. We conclude that both models of chronic stress lead to anxiety-like behavior and decreased amygdalal Na(+), K(+)-ATPase activity, which appears not to be related to oxidative imbalance. The relationship between this decreased activity and anxiety-like behavior remains to be studied.

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Effect of ouabain on sodium pump alpha-isoform expression in an animal model of mania

Cited by 16 publications

References 31 publications

Decreased BDNF levels in amygdala and hippocampus after intracerebroventricular administration of ouabain

Decreased BDNF levels in amygdala and hippocampus after intracerebroventricular administration of ouabain

Effect of repeated restraint stress and clomipramine on Na⁺/K⁺‐ATPase activity and behavior in rats

Na+, K+ ATPase Activity Is Reduced in Amygdala of Rats with Chronic Stress-Induced Anxiety-Like Behavior

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Effect of ouabain on sodium pump alpha-isoform expression in an animal model of mania

Cited by 16 publications

References 31 publications

Decreased BDNF levels in amygdala and hippocampus after intracerebroventricular administration of ouabain

Decreased BDNF levels in amygdala and hippocampus after intracerebroventricular administration of ouabain

Effect of repeated restraint stress and clomipramine on Na+/K+‐ATPase activity and behavior in rats

Na+, K+ ATPase Activity Is Reduced in Amygdala of Rats with Chronic Stress-Induced Anxiety-Like Behavior

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Effect of repeated restraint stress and clomipramine on Na⁺/K⁺‐ATPase activity and behavior in rats