Attenuation of mania-like behavior in Na+,K+-ATPase α3 mutant mice by prospective therapies for bipolar disorder: Melatonin and exercise
Abstract
Bipolar disorder is a neuropsychiatric disease characterized by states of mania with or without depression. Pharmacological treatments can be inadequate at regulating mood for many individuals. Melatonin therapy and aerobic exercise are independent prospective therapies for bipolar disorder that have shown potential as mood stabilizers in humans. Myshkin mice (Myk/+) carry a heterozygous missense mutation in the neuronal Na(+),K(+)-ATPase α3 and model mania-related symptoms of bipolar disorder including increased activity, risk-taking behavior and reductions in sleep. One cohort of Myk/+ and wild-type littermates (+/+) was treated with melatonin and a separate cohort was treated with voluntary exercise. Mania-related behavior was assessed in both cohorts. The effect of melatonin on sleep and the effect of exercise on brain-derived neurotrophic factor (BDNF) expression in the hippocampus were assayed. Melatonin and voluntary wheel running were both effective at reducing mania-related behavior in Myk/+ but did not affect behavior in +/+. Melatonin increased sleep in Myk/+ and did not change sleep in +/+. Myk/+ showed higher baseline levels of BDNF protein in the hippocampus than +/+. Exercise increased BDNF protein in +/+ hippocampus, while it did not significantly affect BDNF levels in Myk/+ hippocampus. These findings support initial studies in humans indicating that melatonin and exercise are useful independent adjunct therapies for bipolar disorder. Their effects on mood regulation should be further examined in randomized clinical trials. Our results also suggest that hippocampal BDNF may not mediate the effects of exercise on mania-related behavior in the Myk/+ model of mania.
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Physical activity augments neuronal protection in brain disorders by stimulating BDNF expression.
“These studies indeed indicated that physical activity augments neuronal protection in brain disorders by stimulating BDNF expression.”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [213]
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- Authors
- Kirshenbaum, G. S., Burgess, C. R., Déry, N., Fahnestock, M., Peever, J. H., & Roder, J. C.
- Affiliations
- Mount Sinai Hospital (CA)
- University of Toronto (CA)
- McMaster University (CA)
- Corresponding author
- Kirshenbaum, G.S.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 260
- Pages
- 195-204
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2061927181
- Cited by
- 33
- References
- 63
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 8 · 2015: 3 · 2014: 3
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (MOP 94856)
- Amalgamated Transit Union
- Ontario Mental Health Foundation
- Natural Sciences and Engineering Research Council
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- bipolar disorder, mania, melatonin, voluntary exercise, wheel running, brain-derived neurotrophic factor, hippocampus, sleep, mood stabilizers, risk-taking
- MeSH terms
- Sodium-Potassium-Exchanging ATPase, Animals, Behavior, Animal, Bipolar Disorder, Disease Models, Animal, Exercise Therapy, Female, Hippocampus, Male, Melatonin, Mice, Inbred C57BL, Mice, Mutant Strains, Motor Activity, Sleep, Brain-Derived Neurotrophic Factor, Mice
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