Aerobic Training and Potential Neurogenesis in Progressive Multiple Sclerosis: Focus on the Hippocampus and the Subventricular Zone
Tetsu Morozumi1, Paola Valsasina4, Paolo Preziosa2, Alessandro Meani4, Rob Motl5, Maria Amato6, Giampaolo Brichetto7, Vincenzo Daniele Boccia8, Jeremy Chataway9, Nancy Chiaravalloti10, Gary Cutter11, Ulrik Dalgas12, John DeLuca10, Rachel Farrell13, Peter Feys14, Jennifer Freeman15, Matilde Inglese16, Cecilia Meza17, Amber Salter18, Brian Sandroff10, Anthony Feinstein17, Massimo Filippi3, Maria Rocca2
1Neuroimaging Research Unit, Division of Neuroscience, 2Neuroimaging Research Unit, Division of Neuroscience, and Neurology Unit, 3Neuroimaging Research Unit, Division of Neuroscience, Neurology Unit, Neurorehabilitation Unit, and Neurophysiology Service, IRCCS San Raffaele Scientific Institute; and Vita-Salute San Raffaele University, 4Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 5Department of Kinesiology and Nutrition, University of Illinois Chicago, 6Department NEUROFARBA, Section Neurosciences, University of Florence; and IRCCS Fondazione Don Carlo Gnocchi, 7AISM Rehabilitation Service, Italian MS Society, 8Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, and Center of Excellence for Biomedical Research, University of Genoa, 9Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, and University College London Hospitals, 10Kessler Foundation, 11Department of Biostatistics, University of Alabama At Birmingham, 12Exercise Biology, Department of Public Health, Aarhus University, 13Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, 14Hasselt University and UMSC Hasselt, 15Faculty of Health, School of Health Professions, University of Plymouth, 16Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, and Center of Excellence for Biomedical Research, University of Genoa and IRCCS Ospedale Policlinico San Martino, 17Department of Psychiatry, University of Toronto and Sunnybrook Health Sciences Centre, 18Department of Neurology, Section on Statistical Planning and Analysis, UT Southwestern Medical Center
Objective:
To assess the effects of aerobic exercise on the volume of the hippocampus and its subfields and on diffusivity measures of the subventricular zone (SVZ) in patients with progressive multiple sclerosis (MS).
Background:
Neurogenesis may occur in the dentate gyrus (DG) of the hippocampus and the SVZ in the adult mammalian brain. In MS patients, aerobic training may exert a neuroprotective role on the brain by stimulating neurogenesis in DG and SVZ, which could translate into measurable volumetric or microstructural alterations within these two regions, but further evidence is needed to confirm this hypothesis.
Design/Methods:
We retrospectively analyzed data from 84 patients with progressive MS enrolled at four sites participating in the CogEx MRI substudy. Thirty-nine patients performed aerobic training, while 45 patients undertook a balance- and stretching-based sham exercise intervention. Both groups trained twice weekly for twelve weeks. At baseline, post-intervention and six-month follow-up, patients underwent MRI assessment on a 3.0 T scanner. FreeSurfer’s longitudinal processing stream was used to analyze hippocampal subfields’ volumes. Fractional anisotropy and mean diffusivity were extracted from the SVZ and the thalamus (as control region).
Results:
There were no differences between the two groups in the assessed variables at baseline (p≥0.070). The DG showed a significant volume increase post-intervention in the aerobic exercise group (mean change=0.63%, 95% confidence interval [95%CI]=0.04%;1.22%, p=0.035), but not in the sham group (mean change=-0.26%, 95%CI=-0.81%;0.28%, p=0.337). DG volume increase was significantly greater in the aerobic group compared to the sham group (p=0.029). No significant volumetric changes were found in the other hippocampal subfields nor in the diffusivity metrics of the SVZ (p≥0.057). No significant changes in either group were found between end of training and the six-month follow-up (p≥0.061)
Conclusions:
Aerobic exercise increases DG volume in progressive MS patients but does not modify microstructural integrity of the SVZ.
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