Attenuation of mania-like behavior in Na+,K+-ATPase α3 mutant mice by prospective therapies for bipolar disorder: Melatonin and exercise

Kirshenbaum, Greer S.; Burgess, Christian R.; Déry, Nicolas; Fahnestock, Margaret; Peever, John H.; Roder, John

doi:10.1016/j.neuroscience.2013.12.011

Cited by 29 publications

(21 citation statements)

References 55 publications

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“…Chronic treatment with lithium or valproic acid normalized only the anxiety and hyperactivity phenotypes (Kirshenbaum et al, 2012). Interestingly, adjunct therapies for BD and other mood disorders, including exercise and melatonin, are effective for reversing mania-like behaviors in Myk/+ mice (Ng et al, 2007, Kucyi et al, 2010, Kirshenbaum et al, 2012, Sylvia et al, 2012, Kirshenbaum et al, 2014). More than a month of running wheel access or chronic treatment with melatonin supplementation improved sleep quality and reduced locomotor activity and normalized anxiety related behaviors in these mice (Kirshenbaum et al, 2014), suggesting these mice as a relevant model for studying the potential mechanisms underlying the therapeutic effects of these treatments.…”

Section: Genetic Models Of Bipolar Maniamentioning

confidence: 99%

Animal models of bipolar mania: The past, present and future

2016

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Bipolar disorder (BD) is the sixth leading cause of disability in the world according to the World Health Organization and affects nearly 6 million (~2.5% of the population) adults in the United State alone each year. BD is primarily characterized by mood cycling of depressive (e.g., helplessness, reduced energy and activity, and anhedonia) and manic (e.g., increased energy and hyperactivity, reduced need for sleep, impulsivity, reduced anxiety and depression), episodes. The following review describes several animal models of bipolar mania with a focus on more recent findings using genetically modified mice, including several with the potential of investigating the mechanisms underlying ‘mood’ cycling (or behavioral switching in rodents). We discuss whether each of these models satisfy criteria of validity (i.e., face, predictive, and construct), while highlighting their strengths and limitations. Animal models are helping to address critical questions related to pathophysiology of bipolar mania, in an effort to more clearly define necessary targets of first-line medications, lithium and valproic acid, and to discover novel mechanisms with the hope of developing more effective therapeutics. Future studies will leverage new technologies and strategies for integrating animal and human data to reveal important insights into the etiology, pathophysiology, and treatment of BD.

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Section: Genetic Models Of Bipolar Maniamentioning

confidence: 99%

Animal models of bipolar mania: The past, present and future

2016

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“…Because the negative impact of maternal isolation on postpartum mothers is not well understood compared to offspring, increased PPD after maternal isolation is also remarkable. Importantly, it has been suggested that changes in the activity of Na + , K + -ATPase are involved in psychiatric diseases including bipolar disorder (44, 45). Focusing on the specific molecular pathways related to each disease is very important in future research.…”

Section: Estrogen and Postpartum Depressionmentioning

confidence: 99%

The Role of Brain-Derived Neurotrophic Factor in Comorbid Depression: Possible Linkage with Steroid Hormones, Cytokines, and Nutrition

et al. 2014

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Increasing evidence demonstrates a connection between growth factor function (including brain-derived neurotrophic factor, BDNF), glucocorticoid levels (one of the steroid hormones), and the pathophysiology of depressive disorders. Because both BDNF and glucocorticoids regulate synaptic function in the central nervous system, their functional interaction is of major concern. Interestingly, alterations in levels of estrogen, another steroid hormone, may play a role in depressive-like behavior in postpartum females with fluctuations of BDNF-related molecules in the brain. BDNF and cytokines, which are protein regulators of inflammation, stimulate multiple intracellular signaling cascades involved in neuropsychiatric illness. Pro-inflammatory cytokines may increase vulnerability to depressive symptoms, such as the increased risk observed in patients with cancer and/or autoimmune diseases. In this review, we discuss the possible relationship between inflammation and depression, in addition to the cross-talk among cytokines, BDNF, and steroids. Further, since nutritional status has been shown to affect critical pathways involved in depression through both BDNF function and the monoamine system, we also review current evidence surrounding diet and supplementation (e.g., flavonoids) on BDNF-mediated brain functions.

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“…The significant association with BD of six single SNPs in the three genes of the Na + , K + -ATPase α isoforms, suggests that this enzyme plays a role in the etiology of the disease [78]. It was also shown that a genetic dysfunction of the neuron-specific Na + , K + -ATPase α3 isoform (Myshkin mice) induces manic-like behavior [79]. …”

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

confidence: 99%

Na+, K+-ATPase Signaling and Bipolar Disorder

Lichtstein¹,

Ilani²,

Rosen³

et al. 2018

IJMS

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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.

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Attenuation of mania-like behavior in Na+,K+-ATPase α3 mutant mice by prospective therapies for bipolar disorder: Melatonin and exercise

Cited by 29 publications

References 55 publications

Animal models of bipolar mania: The past, present and future

Animal models of bipolar mania: The past, present and future

The Role of Brain-Derived Neurotrophic Factor in Comorbid Depression: Possible Linkage with Steroid Hormones, Cytokines, and Nutrition

Na+, K+-ATPase Signaling and Bipolar Disorder

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