PMID- 24342563
OWN - NLM
STAT- MEDLINE
DCOM- 20140925
LR  - 20220321
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 260
DP  - 2014 Feb 28
TI  - Attenuation of mania-like behavior in Na(+),K(+)-ATPase alpha3 mutant mice by 
      prospective therapies for bipolar disorder: melatonin and exercise.
PG  - 195-204
LID - S0306-4522(13)01020-8 [pii]
LID - 10.1016/j.neuroscience.2013.12.011 [doi]
AB  - 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 alpha3 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.
CI  - Copyright (c) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Kirshenbaum, G S
AU  - Kirshenbaum GS
AD  - Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 
      1X5, Canada; Institute of Medical Science, University of Toronto, Toronto, 
      Ontario M5S 1A8, Canada. Electronic address: greershelby@gmail.com.
FAU - Burgess, C R
AU  - Burgess CR
AD  - Cell and System Biology, University of Toronto, Toronto, Ontario M5S 3G3, Canada.
FAU - Dery, N
AU  - Dery N
AD  - Department of Psychology, Neuroscience and Behavior, McMaster University, 
      Hamilton, Ontario L8N 3Z5, Canada.
FAU - Fahnestock, M
AU  - Fahnestock M
AD  - Department of Psychiatry and Behavioral Neurosciences, McMaster University, 
      Hamilton, Ontario L8N 3Z5, Canada.
FAU - Peever, J H
AU  - Peever JH
AD  - Cell and System Biology, University of Toronto, Toronto, Ontario M5S 3G3, Canada.
FAU - Roder, J C
AU  - Roder JC
AD  - Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 
      1X5, Canada; Institute of Medical Science, University of Toronto, Toronto, 
      Ontario M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, 
      Toronto, Ontario M5S 1A8, Canada.
LA  - eng
GR  - MOP94856/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131214
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 3.6.1.- (Atp1a3 protein, mouse)
RN  - EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase)
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Bipolar Disorder/drug therapy/*therapy
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Disease Models, Animal
MH  - *Exercise Therapy
MH  - Female
MH  - Hippocampus/drug effects
MH  - Male
MH  - Melatonin/*therapeutic use
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Motor Activity/drug effects
MH  - Sleep/drug effects
MH  - Sodium-Potassium-Exchanging ATPase/*genetics
OTO - NOTNLM
OT  - ANOVA
OT  - Atp1a3
OT  - BDNF
OT  - EDTA
OT  - EEG
OT  - ELISA
OT  - EMG
OT  - ENU
OT  - EPM
OT  - LDB
OT  - Myk
OT  - Myshkin
OT  - N-ethyl-N-nitrosourea
OT  - Na(+),K(+)-ATPase alpha3
OT  - REM
OT  - RT-PCR
OT  - SEM
OT  - analysis of variance
OT  - bipolar disorder
OT  - brain-derived neurotrophic factor
OT  - electroencephalographic
OT  - electromyographic
OT  - elevated plus maze
OT  - enzyme-linked immunosorbent assay
OT  - ethylenediaminetetraacetic acid
OT  - light-dark box
OT  - mania
OT  - melatonin
OT  - rapid eye movement
OT  - real-time polymerase chain reaction
OT  - standard error of mean
OT  - voluntary exercise
EDAT- 2013/12/18 06:00
MHDA- 2014/09/26 06:00
CRDT- 2013/12/18 06:00
PHST- 2013/10/15 00:00 [received]
PHST- 2013/11/21 00:00 [revised]
PHST- 2013/12/04 00:00 [accepted]
PHST- 2013/12/18 06:00 [entrez]
PHST- 2013/12/18 06:00 [pubmed]
PHST- 2014/09/26 06:00 [medline]
AID - S0306-4522(13)01020-8 [pii]
AID - 10.1016/j.neuroscience.2013.12.011 [doi]
PST - ppublish
SO  - Neuroscience. 2014 Feb 28;260:195-204. doi: 10.1016/j.neuroscience.2013.12.011. 
      Epub 2013 Dec 14.