Effect of enhanced voluntary physical exercise on brain levels of monoamines in Huntington disease mice

Using the R6/1 mouse model of Huntington disease (HD), we have recently shown that voluntary physical activity was able to correct the depressive-like behaviours exhibited by the HD animals at a pre-motor symptomatic stage of the disease. Using the high performance liquid chromatography system, we have now evaluated the effect of exercise on monoamine metabolism in HD mice. We found that serotonin and its metabolite as well as dopamine and noradrenaline were reduced across several brain regions in female R6/1 animals. Our data also suggest that some of these neurochemical deficits were modulated by physical activity, in a genotype-region dependent manner. These newly identified changes could account for some of the behavioural effects of exercise previously reported in HD mice.

[1]  A. Klintsova,et al.  Long-Term Consequences of Developmental Alcohol Exposure on Brain Structure and Function: Therapeutic Benefits of Physical Activity , 2012, Brain sciences.

[2]  L. Lanfumey,et al.  Treatment of depressive‐like behaviour in Huntington's disease mice by chronic sertraline and exercise , 2012, British journal of pharmacology.

[3]  L. Lanfumey,et al.  Sexually Dimorphic Serotonergic Dysfunction in a Mouse Model of Huntington's Disease and Depression , 2011, PloS one.

[4]  Jane S. Paulsen,et al.  Assessment of Depression, Anxiety and Apathy in Prodromal and Early Huntington Disease , 2011, PLoS currents.

[5]  N. Wood,et al.  “Brain training” improves cognitive performance and survival in a transgenic mouse model of Huntington's disease , 2011, Neurobiology of Disease.

[6]  R. Schiffmann,et al.  Altered Dopamine and Serotonin Metabolism in Motorically Asymptomatic R6/2 Mice , 2011, PloS one.

[7]  H. Bönisch,et al.  Depression and antidepressants: insights from knockout of dopamine, serotonin or noradrenaline re-uptake transporters. , 2011, Pharmacology & therapeutics.

[8]  H. van Praag,et al.  Exercise is not beneficial and may accelerate symptom onset in a mouse model of Huntington’s disease , 2010, PLoS currents.

[9]  B. Leavitt,et al.  The Clinical and Genetic Features of Huntington Disease , 2010, Journal of geriatric psychiatry and neurology.

[10]  D. Velakoulis,et al.  A retrospective study of the impact of lifestyle on age at onset of Huntington disease , 2010, Movement disorders : official journal of the Movement Disorder Society.

[11]  P. Blier,et al.  Prospect of a dopamine contribution in the next generation of antidepressant drugs: the triple reuptake inhibitors. , 2009, Current drug targets.

[12]  A. Bjørnebekk,et al.  The antidepressant effects of running and escitalopram are associated with levels of hippocampal NPY and Y1 receptor but not cell proliferation in a rat model of depression , 2009, Hippocampus.

[13]  A. Hannan,et al.  Altered serotonin receptor expression is associated with depression-related behavior in the R6/1 transgenic mouse model of Huntington's disease. , 2009, Human molecular genetics.

[14]  K. Lesch,et al.  Differential long-term effects of MDMA on the serotoninergic system and hippocampal cell proliferation in 5-HTT knock-out vs. wild-type mice. , 2008, The international journal of neuropsychopharmacology.

[15]  M. Hayden,et al.  Prevention of depressive behaviour in the YAC128 mouse model of Huntington disease by mutation at residue 586 of huntingtin. , 2008, Brain : a journal of neurology.

[16]  C. Blakemore,et al.  Wheel running from a juvenile age delays onset of specific motor deficits but does not alter protein aggregate density in a mouse model of Huntington's disease , 2008, BMC Neuroscience.

[17]  Jess Nithianantharajah,et al.  Gene–environment interactions modulating cognitive function and molecular correlates of synaptic plasticity in Huntington’s disease transgenic mice , 2008, Neurobiology of Disease.

[18]  Jane S. Paulsen,et al.  Psychiatric Symptoms in Huntington’s Disease before Diagnosis: The Predict-HD Study , 2007, Biological Psychiatry.

[19]  A. Schene,et al.  Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies , 2007, Molecular Psychiatry.

[20]  Nathan C. Stam,et al.  Differential effects of voluntary physical exercise on behavioral and brain-derived neurotrophic factor expression deficits in huntington’s disease transgenic mice , 2006, Neuroscience.

[21]  D. Craufurd,et al.  Psychiatric disorders in preclinical Huntington’s disease , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[22]  Jane S. Paulsen,et al.  Depression and stages of Huntington's disease. , 2005, The Journal of neuropsychiatry and clinical neurosciences.

[23]  G. Mengod,et al.  Brain‐derived neurotrophic factor modulates dopaminergic deficits in a transgenic mouse model of Huntington's disease , 2005, Journal of neurochemistry.

[24]  C. Cotman,et al.  Voluntary exercise protects against stress-induced decreases in brain-derived neurotrophic factor protein expression , 2004, Neuroscience.

[25]  S. Maier,et al.  Freewheel Running Prevents Learned Helplessness/Behavioral Depression: Role of Dorsal Raphe Serotonergic Neurons , 2003, The Journal of Neuroscience.

[26]  P. Brundin,et al.  Evidence for Dysfunction of the Nigrostriatal Pathway in the R6/1 Line of Transgenic Huntington's Disease Mice , 2002, Neurobiology of Disease.

[27]  W. Strawbridge,et al.  Physical activity reduces the risk of subsequent depression for older adults. , 2002, American journal of epidemiology.

[28]  James A. Blumenthal,et al.  Exercise Treatment for Major Depression: Maintenance of Therapeutic Benefit at 10 Months , 2000, Psychosomatic medicine.

[29]  B. Toone,et al.  Homocysteine, folate, methylation, and monoamine metabolism in depression , 2000, Journal of neurology, neurosurgery, and psychiatry.

[30]  Colin Blakemore,et al.  Delaying the onset of Huntington's in mice , 2000, Nature.

[31]  S. W. Davies,et al.  Altered neurotransmitter receptor expression in transgenic mouse models of Huntington's disease. , 1999, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[32]  S. W. Davies,et al.  Brain Neurotransmitter Deficits in Mice Transgenic for the Huntington’s Disease Mutation , 1999, Journal of neurochemistry.

[33]  M. Åsberg,et al.  Neurotransmitters and Suicidal Behavior , 1997, Annals of the New York Academy of Sciences.

[34]  S. W. Davies,et al.  Exon 1 of the HD Gene with an Expanded CAG Repeat Is Sufficient to Cause a Progressive Neurological Phenotype in Transgenic Mice , 1996, Cell.

[35]  D. Brooks,et al.  Striatal D1 and D2 dopamine receptor loss in asymptomatic mutation carriers of Huntington's disease , 1996, Annals of neurology.

[36]  Manish S. Shah,et al.  A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes , 1993, Cell.

[37]  X. Beristain,et al.  Specific psychiatric manifestations among preclinical Huntington disease mutation carriers. , 2007, Archives of neurology.

[38]  M. Trivedi,et al.  Exercise treatment for depression: efficacy and dose response. , 2005, American journal of preventive medicine.

[39]  L. Solberg,et al.  Circadian rhythms and depression: effects of exercise in an animal model. , 1999, The American journal of physiology.