Intensive Rehabilitation Increases BDNF Serum Levels in Parkinsonian Patients

Background. Exercise may decrease the risk of Parkinson’s disease (PD) in humans and reduce PD symptoms in animal models. The beneficial effects have been linked to increased levels of neurotrophic factors. Objective. We examined whether intensive rehabilitation treatment reduces motor disability in patients in the early stages of PD and increases brain-derived neurotrophic factor (BDNF) serum levels. Methods. Thirty participants in the early stages of PD treated with rasagiline were randomly assigned to 3 hours of rehabilitation treatment that included aerobic exercise for 28 days (Group 1) or to not therapy (control; Group 2). BDNF serum levels were assessed at time T0 (baseline, before treatment), T1 (10 days), T2 (20 days), and T3 (28 days). At T0 and T3, we assessed the Unified Parkinson’s Disease Rating Scale (UPDRS) III in both groups, as well as the UPDRS II and total, Berg Balance Scale, and 6-minute walking test only in Group 1. Results. BDNF levels significantly increased at T1 in Group 1, an increase that was maintained throughout the treatment period. At T3 compared to T0, UPDRS III scores significantly improved in Group 1 along with scores for UPDRS II, total, Berg Balance Scale, and 6-minute walking test. Conclusions. Intensive rehabilitation treatment increases the BDNF levels and improves PD signs in patients in the early stages of the disease. These results are in line with studies on animal models of PD and healthy subjects.

[1]  J. Ahlskog Does vigorous exercise have a neuroprotective effect in Parkinson disease? , 2011, Neurology.

[2]  Roberto Maestri,et al.  Rehabilitation treatment of gait in patients with Parkinson's disease with freezing: A comparison between two physical therapy protocols using visual and auditory cues with or without treadmill training , 2009, Movement disorders : official journal of the Movement Disorder Society.

[3]  D. Thurman,et al.  How common are the “common” neurologic disorders? , 2007, Neurology.

[4]  B. E. Maki,et al.  Measuring balance in the elderly: validation of an instrument. , 1992, Canadian journal of public health = Revue canadienne de sante publique.

[5]  Monica Fabiani,et al.  Neuroanatomical correlates of aging, cardiopulmonary fitness level, and education. , 2008, Psychophysiology.

[6]  D. Katz,et al.  Effectiveness of an Inpatient Multidisciplinary Rehabilitation Program for People With Parkinson Disease , 2008, Physical Therapy.

[7]  Rebecca Stowe,et al.  Physiotherapy versus placebo or no intervention in Parkinson's disease. , 2012, The Cochrane database of systematic reviews.

[8]  田尻 直輝,et al.  Exercise exerts neuroprotective effects on Parkinson's disease model of rats , 2010 .

[9]  G. Miller,et al.  Exercise induces behavioral recovery and attenuates neurochemical deficits in rodent models of Parkinson's disease , 2003, Neuroscience.

[10]  G. Akopian,et al.  Enhancing neuroplasticity in the basal ganglia: The role of exercise in Parkinson's disease , 2010, Movement disorders : official journal of the Movement Disorder Society.

[11]  G. Kwakkel,et al.  Measuring gait and gait-related activities in Parkinson's patients own home environment: a reliability, responsiveness and feasibility study. , 2005, Parkinsonism & related disorders.

[12]  Stuart Maudsley,et al.  A neural signaling triumvirate that influences ageing and age-related disease: insulin/IGF-1, BDNF and serotonin , 2004, Ageing Research Reviews.

[13]  Carl W. Cotman,et al.  Exercise builds brain health: key roles of growth factor cascades and inflammation , 2007, Trends in Neurosciences.

[14]  C. Marsden,et al.  Recent Developments in Parkinson's Disease , 1986 .

[15]  W. Weiner,et al.  The clinically important difference on the unified Parkinson's disease rating scale. , 2010, Archives of neurology.

[16]  G. Knudsen,et al.  Striatal dopamine transporter binding correlates with serum BDNF levels in patients with striatal dopaminergic neurodegeneration , 2012, Neurobiology of Aging.

[17]  Chris J. McBain,et al.  The Role of the GluR2 Subunit in AMPA Receptor Function and Synaptic Plasticity , 2007, Neuron.

[18]  Glen E Duncan,et al.  Effects of aerobic exercise on mild cognitive impairment: a controlled trial. , 2010, Archives of neurology.

[19]  A. Schatzkin,et al.  Physical activities and future risk of Parkinson disease , 2010, Neurology.

[20]  A. Gentile,et al.  Improving gait and promoting retention in individuals with Parkinson’s disease: a pilot study , 2010, Journal of Neurology.

[21]  John D Sorkin,et al.  Randomized clinical trial of 3 types of physical exercise for patients with Parkinson disease. , 2013, JAMA neurology.

[22]  R. Leahy,et al.  Exercise elevates dopamine D2 receptor in a mouse model of Parkinson's disease: In vivo imaging with [18F]fallypride , 2010, Movement disorders : official journal of the Movement Disorder Society.

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

[24]  David J. Brooks,et al.  Progression of monoaminergic dysfunction in Parkinson's disease: A longitudinal 18F-dopa PET study , 2011, NeuroImage.

[25]  A. Teixeira,et al.  Serum levels of brain-derived neurotrophic factor correlate with motor impairment in Parkinson’s disease , 2010, Journal of Neurology.

[26]  Theodore Garland,et al.  Exercise increases hippocampal neurogenesis to high levels but does not improve spatial learning in mice bred for increased voluntary wheel running. , 2003, Behavioral neuroscience.

[27]  F. Gage,et al.  Functional neurogenesis in the adult hippocampus , 2002, Nature.

[28]  Ya-Ting Chang,et al.  Treadmill exercise counteracts the suppressive effects of peripheral lipopolysaccharide on hippocampal neurogenesis and learning and memory , 2007, Journal of neurochemistry.

[29]  B. Sakmann,et al.  Relative abundance of subunit mRNAs determines gating and Ca2+ permeability of AMPA receptors in principal neurons and interneurons in rat CNS , 1995, Neuron.

[30]  Pietro Balbi,et al.  Effectiveness of Intensive Inpatient Rehabilitation Treatment on Disease Progression in Parkinsonian Patients , 2012, Neurorehabilitation and neural repair.

[31]  S. Gilman,et al.  Diagnostic criteria for Parkinson disease. , 1999, Archives of neurology.

[32]  Orna Zagoory-Sharon,et al.  Oxytocin and cortisol in romantically unattached young adults: associations with bonding and psychological distress. , 2008, Psychophysiology.

[33]  V. Preedy,et al.  Unified Parkinson's Disease Rating Scale , 2010 .

[34]  Yuen-Sum Lau,et al.  Neuroprotective effects and mechanisms of exercise in a chronic mouse model of Parkinson’s disease with moderate neurodegeneration , 2011, The European journal of neuroscience.

[35]  S. Lehéricy,et al.  Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease. , 2010, The Journal of clinical investigation.

[36]  W. Spirduso,et al.  Endurance training effects on striatal D2 dopamine receptor binding and striatal dopamine metabolite levels , 1987, Neuroscience Letters.

[37]  B. Fisher,et al.  Exercise‐induced behavioral recovery and neuroplasticity in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐lesioned mouse basal ganglia , 2004, Journal of neuroscience research.

[38]  Tzu-Feng Wang,et al.  Running exercise protects the substantia nigra dopaminergic neurons against inflammation-induced degeneration via the activation of BDNF signaling pathway , 2011, Brain, Behavior, and Immunity.

[39]  Jeffrey M. Hausdorff,et al.  Six weeks of intensive treadmill training improves gait and quality of life in patients with Parkinson's disease: a pilot study. , 2007, Archives of physical medicine and rehabilitation.

[40]  William A Banks,et al.  Transport of brain-derived neurotrophic factor across the blood–brain barrier , 1998, Neuropharmacology.

[41]  M. Febbraio,et al.  Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase , 2009, Diabetologia.

[42]  E. McAuley,et al.  Frontiers in Aging Neuroscience Aging Neuroscience , 2022 .

[43]  Sebastião Gobbi,et al.  Physical exercise modulates peripheral levels of brain-derived neurotrophic factor (BDNF): a systematic review of experimental studies in the elderly. , 2013, Archives of gerontology and geriatrics.

[44]  O. Lindvall,et al.  Effects of brain-derived neurotrophic factor on neuronal structure of dopaminergic neurons in dissociated cultures of human fetal mesencephalon , 1996, Experimental Brain Research.

[45]  Adrian H. Taylor,et al.  The effectiveness of exercise interventions for people with Parkinson's disease: A systematic review and meta‐analysis , 2008, Movement disorders : official journal of the Movement Disorder Society.

[46]  Jeffrey M. Hausdorff,et al.  Falls and freezing of gait in Parkinson's disease: A review of two interconnected, episodic phenomena , 2004, Movement disorders : official journal of the Movement Disorder Society.

[47]  T. Joh,et al.  Neuroprotection and Neuronal Differentiation Studies Using Substantia Nigra Dopaminergic Cells Derived from Transgenic Mouse Embryos , 1999, The Journal of Neuroscience.

[48]  E. Bézard,et al.  Animal models of Parkinson's disease: Limits and relevance to neuroprotection studies , 2013, Movement disorders : official journal of the Movement Disorder Society.