Diffusion tensor-MRI detects exercise-induced neuroplasticity in the hippocampal microstructure in mice

Background: Despite considerable research on exercise-induced neuroplasticity in the brain, a major ongoing challenge in translating findings from animal studies to humans is that clinical and preclinical settings employ very different techniques. Objective: Here we aim to bridge this divide by using diffusion tensor imaging MRI (DTI), an advanced imaging technique commonly applied in human studies, in a longitudinal exercise study with mice. Methods: Wild-type mice were exercised using voluntary free-wheel running, and MRI scans were at baseline and after four weeks and nine weeks of running. Results: Both hippocampal volume and fractional anisotropy, a surrogate for microstructural directionality, significantly increased with exercise. In addition, exercise levels correlated with effect size. Histological analysis showed more PDGFRα+ oligodendrocyte precursor cells in the corpus callosum of running mice. Conclusions: These results provide compelling in vivo support for the concept that similar adaptive changes occur in the brains of mice and humans in response to exercise.

[1]  R. Hill,et al.  Myelin plasticity in adulthood and aging , 2019, Neuroscience Letters.

[2]  Andrew J. Mocle,et al.  Disruption of Oligodendrogenesis Impairs Memory Consolidation in Adult Mice , 2019, Neuron.

[3]  C. Stern,et al.  Improving fitness increases dentate gyrus/CA3 volume in the hippocampal head and enhances memory in young adults , 2020, Hippocampus.

[4]  Bao-Ming Li,et al.  Voluntary wheel running promotes myelination in the motor cortex through Wnt signaling in mice , 2019, Molecular Brain.

[5]  K. Arai,et al.  Treadmill Exercise Suppresses Cognitive Decline and Increases White Matter Oligodendrocyte Precursor Cells in a Mouse Model of Prolonged Cerebral Hypoperfusion , 2019, Translational Stroke Research.

[6]  John-Paul J. Yu,et al.  Exercise ameliorates deficits in neural microstructure in a Disc1 model of psychiatric illness. , 2019, Magnetic resonance imaging.

[7]  D. Centonze,et al.  Voluntary running wheel attenuates motor deterioration and brain damage in cuprizone-induced demyelination , 2019, Neurobiology of Disease.

[8]  Yasuhiro R. Tanaka,et al.  Motor learning requires myelination to reduce asynchrony and spontaneity in neural activity , 2019, Glia.

[9]  G. Rizzo,et al.  Microstructural characterization of corticospinal tract in subacute and chronic stroke patients with distal lesions by means of advanced diffusion MRI , 2019, Neuroradiology.

[10]  Michael I Miller,et al.  Magnetic resonance imaging of mouse brain networks plasticity following motor learning , 2019, PloS one.

[11]  Arthur F. Kramer,et al.  Physical Activity Increases White Matter Microstructure in Children , 2018, Front. Neurosci..

[12]  Emiri T. Mandeville,et al.  A‐Kinase Anchor Protein 12 Is Required for Oligodendrocyte Differentiation in Adult White Matter , 2018, Stem cells.

[13]  Janice A. Zawaski,et al.  Exercise ameliorates neurocognitive impairments in a translational model of pediatric radiotherapy , 2018, Neuro-oncology.

[14]  H. van Praag,et al.  On the Run for Hippocampal Plasticity. , 2018, Cold Spring Harbor perspectives in medicine.

[15]  Frederik Barkhof,et al.  Imaging outcome measures for progressive multiple sclerosis trials , 2017, Multiple sclerosis.

[16]  C. Rosano,et al.  Long-term changes in time spent walking and subsequent cognitive and structural brain changes in older adults , 2017, Neurobiology of Aging.

[17]  J. Guralnik,et al.  Hippocampal Response to a 24-Month Physical Activity Intervention in Sedentary Older Adults. , 2017, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[18]  Susumu Mori,et al.  The role of myelination in measures of white matter integrity: Combination of diffusion tensor imaging and two-photon microscopy of CLARITY intact brains , 2017, NeuroImage.

[19]  W. Richardson,et al.  Rapid production of new oligodendrocytes is required in the earliest stages of motor skill learning , 2016, Nature Neuroscience.

[20]  Bimal Lakhani,et al.  Motor Skill Acquisition Promotes Human Brain Myelin Plasticity , 2016, Neural plasticity.

[21]  Carmen Vivar,et al.  Running rewires the neuronal network of adult-born dentate granule cells , 2016, NeuroImage.

[22]  Simone Kühn,et al.  Changes in fitness are associated with changes in hippocampal microstructure and hippocampal volume among older adults , 2016, NeuroImage.

[23]  Thomas E. Nichols,et al.  Multi-modal characterization of rapid anterior hippocampal volume increase associated with aerobic exercise , 2016, NeuroImage.

[24]  Heidi Johansen-Berg,et al.  A systematic review of MRI studies examining the relationship between physical fitness and activity and the white matter of the ageing brain , 2016, NeuroImage.

[25]  Arthur F. Kramer,et al.  White matter microstructure mediates the relationship between cardiorespiratory fitness and spatial working memory in older adults , 2016, NeuroImage.

[26]  Emrah Duzel,et al.  Can physical exercise in old age improve memory and hippocampal function? , 2016, Brain : a journal of neurology.

[27]  Derek K. Jones,et al.  Myelination of the right parahippocampal cingulum is associated with physical activity in young healthy adults , 2016, Brain Structure and Function.

[28]  W. Richardson,et al.  Oligodendrocyte Development and Plasticity. , 2016, Cold Spring Harbor perspectives in biology.

[29]  Nick C Fox,et al.  Diffusion imaging changes in grey matter in Alzheimer’s disease: a potential marker of early neurodegeneration , 2015, Alzheimer's Research & Therapy.

[30]  John G. Sled,et al.  MRI-detectable changes in mouse brain structure induced by voluntary exercise , 2015, NeuroImage.

[31]  Jan Scholz,et al.  Rotarod training in mice is associated with changes in brain structure observable with multimodal MRI , 2015, NeuroImage.

[32]  P. Gass,et al.  The hippocampus and exercise: histological correlates of MR-detected volume changes , 2016, Brain Structure and Function.

[33]  William D. Richardson,et al.  Motor skill learning requires active central myelination , 2014, Science.

[34]  H. Heinze,et al.  Vascular hippocampal plasticity after aerobic exercise in older adults , 2014, Molecular Psychiatry.

[35]  J. Hodges,et al.  Beyond the temporal pole: limbic memory circuit in the semantic variant of primary progressive aphasia. , 2014, Brain : a journal of neurology.

[36]  Christian Keysers,et al.  Inter‐individual differences in audio‐motor learning of piano melodies and white matter fiber tract architecture , 2014, Human brain mapping.

[37]  T. Liu-Ambrose,et al.  Aerobic exercise increases hippocampal volume in older women with probable mild cognitive impairment: a 6-month randomised controlled trial , 2014, British Journal of Sports Medicine.

[38]  A. Sartorius,et al.  Exercise boosts hippocampal volume by preventing early age‐related gray matter loss , 2014, Hippocampus.

[39]  Heidi Johansen-Berg,et al.  Motor Skill Learning Induces Changes in White Matter Microstructure and Myelination , 2013, The Journal of Neuroscience.

[40]  Edward McAuley,et al.  The influence of aerobic fitness on cerebral white matter integrity and cognitive function in older adults: Results of a one‐year exercise intervention , 2013, Human brain mapping.

[41]  L. Bherer,et al.  A Review of the Effects of Physical Activity and Exercise on Cognitive and Brain Functions in Older Adults , 2013, Journal of aging research.

[42]  Thomas R. Knösche,et al.  White matter integrity, fiber count, and other fallacies: The do's and don'ts of diffusion MRI , 2013, NeuroImage.

[43]  Helgi B. Schiöth,et al.  Association between physical activity and brain health in older adults , 2013, Neurobiology of Aging.

[44]  A. Rosenzweig,et al.  Can Exercise Teach Us How to Treat Heart Disease? , 2012, Circulation.

[45]  I. Deary,et al.  Neuroprotective lifestyles and the aging brain , 2012, Neurology.

[46]  J. Rhodes,et al.  Aerobic exercise is the critical variable in an enriched environment that increases hippocampal neurogenesis and water maze learning in male C57BL/6J mice , 2012, Neuroscience.

[47]  Lei Zheng,et al.  In vivo voxel based morphometry: Detection of increased hippocampal volume and decreased glutamate levels in exercising mice , 2012, NeuroImage.

[48]  Yaniv Assaf,et al.  Learning in the Fast Lane: New Insights into Neuroplasticity , 2012, Neuron.

[49]  Chobok Kim,et al.  Cardiorespiratory fitness is positively correlated with cerebral white matter integrity in healthy seniors , 2012, NeuroImage.

[50]  Noriko Osumi,et al.  Differential Proliferation Rhythm of Neural Progenitor and Oligodendrocyte Precursor Cells in the Young Adult Hippocampus , 2011, PloS one.

[51]  Y. Shaham,et al.  Running is the neurogenic and neurotrophic stimulus in environmental enrichment. , 2011, Learning & memory.

[52]  Veronique D. Bohbot,et al.  Maze training in mice induces MRI-detectable brain shape changes specific to the type of learning , 2011, NeuroImage.

[53]  E. McAuley,et al.  Exercise training increases size of hippocampus and improves memory , 2011, Proceedings of the National Academy of Sciences.

[54]  Arthur F. Kramer,et al.  A neuroimaging investigation of the association between aerobic fitness, hippocampal volume, and memory performance in preadolescent children , 2010, Brain Research.

[55]  M. Styner,et al.  Aerobic fitness and obesity: relationship to cerebral white matter integrity in the brain of active and sedentary older adults , 2010, British Journal of Sports Medicine.

[56]  Lisa M. Saksida,et al.  Running enhances spatial pattern separation in mice , 2010, Proceedings of the National Academy of Sciences.

[57]  Lynn Rochester,et al.  Motor learning in Parkinson's disease: limitations and potential for rehabilitation. , 2009, Parkinsonism & related disorders.

[58]  Timothy Edward John Behrens,et al.  Training induces changes in white matter architecture , 2009, Nature Neuroscience.

[59]  Elizabeth Gould,et al.  Running induces widespread structural alterations in the hippocampus and entorhinal cortex , 2007, Hippocampus.

[60]  H. Eichenbaum,et al.  The medial temporal lobe and recognition memory. , 2007, Annual review of neuroscience.

[61]  Fred H. Gage,et al.  An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus , 2007, Proceedings of the National Academy of Sciences.

[62]  D. Amaral,et al.  The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies). , 2007, Progress in brain research.

[63]  B. Christie,et al.  Voluntary exercise alters the cytoarchitecture of the adult dentate gyrus by increasing cellular proliferation, dendritic complexity, and spine density , 2005, The Journal of comparative neurology.

[64]  Jun Yoshino,et al.  Demyelination increases radial diffusivity in corpus callosum of mouse brain , 2005, NeuroImage.

[65]  D. Le Bihan Looking into the functional architecture of the brain with diffusion MRI , 2003, Nature reviews. Neuroscience.

[66]  Stephen M. Smith,et al.  A global optimisation method for robust affine registration of brain images , 2001, Medical Image Anal..

[67]  P. Basser,et al.  In vivo fiber tractography using DT‐MRI data , 2000, Magnetic resonance in medicine.

[68]  T J Sejnowski,et al.  Running enhances neurogenesis, learning, and long-term potentiation in mice. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[69]  H. Braak,et al.  Frequency of Stages of Alzheimer-Related Lesions in Different Age Categories , 1997, Neurobiology of Aging.