Abstract
The brain-derived neurotrophic factor (BDNF) is a potent inhibitor of apoptosis-mediated cell death and neurotoxin-induced degeneration of dopaminergic neurons. There is a growing body of evidence implicating BDNF in the pathogenesis of Parkinson’s disease (PD), suggesting it may eventually be used in the development of neuroprotective therapies for PD. The serum BDNF of 47 PD patients and of 23 control subjects was assessed, and serum BNDF levels were significantly decreased in PD patients when compared with controls (p = 0.046). Interestingly enough, BDNF correlated positively with a longer time span of the disease, as well as with the severity of the PD symptoms and with more advanced stages of the disease. Additionally, higher BDNF levels also correlated with poor balance as assessed by the Berg Balance Scale, more time spent at the Timed Up & Go Test, reduced speed of gait and shorter distance walked during the Six-Minute Walk Test. Our results corroborate the literature regarding the involvement of BDNF in PD. We hypothesize that lower BDNF levels in early stages of the disease may be associated with pathogenic mechanisms of PD. The increase of BDNF levels with the progression of the disease may be a compensatory mechanism in more advanced stages of PD.
Similar content being viewed by others
References
Calne D (2005) A definition of Parkinson’s disease. Parkinsonism Relat Disord 11:S39–S40
Binder DK, Scharfman HE (2004) Brain-derived neurotrophic factor. Growth Factors 22:123–131
Schindowski K, Belarbi K, Buée L (2008) Neurotrophic factors in Alzheimer’s disease: role of axonal transport. Genes Brain Behav 7:43–56
Ciammola A, Sassone J, Cannella M et al (2007) Low brain-derived neurotrophic factor (BDNF) levels in serum of Huntington’s disease patients. Am J Med Genet B Neuropsychiatr Genet 144B:574–577
Howells DW, Porritt MJ, Wong JYF et al (2000) Reduced BDNF mRNA expression in the Parkinson’s disease substantia nigra. Exp Neurol 166:127–135
Parain K, Murer MG, Quiao Y et al (1999) Reduced expression of brain-derived neurotrophic factor protein in Parkinson’s disease substantia nigra. Neuroreport 10:557–561
Mogi M, Togaria A, Kondo T et al (1999) Brain-derived growth factor and nerve growth factor concentrations are decreased in the substantia nigra in Parkinson’s disease. Neurosci Lett 270:45–48
Knott C, Stern G, Kingsbury A (2002) Elevated glial brain-derived neurotrophic factor in Parkinson’s diseased nigra. Parkinsonism Relat Disord 8:329–341
Zintzaras E, Hadjigeorgiou GM (2005) The role of G196A polymorphism in the brain-derived neurotrophic factor gene in the cause of Parkinson’s disease: a meta-analysis. J Hum Genet 50:560–566
Levivier M, Przedborski S, Bencsics C, Kang UJ (1995) lntrastriatal implantation of fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevents degeneration of dopaminergic neurons in a rat model of Parkinson’s disease. J Neurosci 15:7810–7820
Mocchetti I, Bachis A, Nosheny RL, Tanda G (2007) Brain-derived neurotrophic factor expression in the substantia nigra does not change after lesions of dopaminergic neurons. Neurotox Res 12:135–143
Trajkovska V, Marcussen AB, Vinberg M et al (2007) Measurements of brain-derived neurotrophic factor: methodological aspects and demographical data. Brain Res Bull 73:143–149
Brucki SMD, Nitrini R, Caramelli P et al (2003) Sugestões para o uso do Mini-Exame do Estado Mental no Brasil. Arq Neuropsiquiatr 61:777–781
Silberman CD, Laks J, Capitão CF (2006) Recognizing depression in patients with Parkinson’s disease: accuracy and specificity of two depression rating scale. Arq Neuropsiquiatr 64:407–411
Tumas V, Rodrigues GGR, Farias TLA, Crippa JAS (2008) The accuracy of diagnosis of major depression in patients with Parkinson’s disease: A comparative study among the UPDRS, the Geriatric Depression Scale and the Beck Depression Inventory. Arq Neuropsiquiatr 66:152–156
Fahn S, Elton R (1987) Unified Parkinson’s Disease Rating Scale. In: Fahn S, Marsden CD, Caine DB, Goldstein M, (eds) Recent developments in Parkinson’s disease, vol 2. Macmillan Health Care information, Florham Park, pp 153–163, 293–304
Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17:427–442
Qutubuddin AA, Pegg PO, Cifu DX et al (2005) Validating the Berg Balance Scale for patients with Parkinson’s disease: a key to rehabilitation evaluation. Arch Phys Med Rehabil 86:789–792
Podsiadlo D, Richardson S (1991) The timed “Up and Go”: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc 39:142–148
Green J, Forster A, Young J (2002) Reliability of gait speed measured by a timed walking test in patients one year after stroke. Clin Rehabil 16:306–314
ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories (2002) ATS statement: guidelines for the six minute walk test. Am J Resp Crit Care Med 166:111–117
Baquet ZC, Bickford PC, Jones KR (2005) Brain-derived neurotrophic factor is required for the establishment of the proper number of dopaminergic neurons in the substantia nigra pars compacta. J Neurosci 25:6251–6259
Porritt MJ, Batchelor PE, Howells DW (2005) Inhibiting BDNF expression by antisense oligonucleotide infusion causes loss of nigral dopaminergic neurons. Exp Neurol 192:226–234
Yasutake C, Kuroda K, Yanagawa T et al (2006) Serum BDNF, TNF-alpha and IL-1beta levels in dementia patients: comparison between Alzheimer’s disease and vascular dementia. Eur Arch Psychiatry Clin Neurosci 256:402–406
Laske C, Stransky E, Leyhe T et al (2006) Stage-dependent BDNF serum concentrations in Alzheimer’s disease. J Neural Transm 113:1217–1224
Gama CS, Andreazza AC, Kunz M et al (2007) Serum levels of brain-derived neurotrophic factor in patients with schizophrenia and bipolar disorder. Neurosci Lett 420:45–48
Reis HJ, Nicolato R, Barbosa IG et al (2008) Increased serum levels of brain-derived neurotrophic factor in chronic institutionalized patients with schizophrenia. Neurosci Lett 439:157–159
Buckley PF, Pillai A, Evans D et al (2007) Brain derived neurotropic factor in first-episode psychosis. Schizophr Res 91:1–5
Sandyk R, Kay SR (1990) The relationship of negative schizophrenia to parkinsonism. Int J Neurosci 55:1–59
Chatterjee A, Chakos M, Koreen A et al (1995) Prevalence and clinical correlates of extrapyramidal signs and spontaneous dyskinesia in never-medicated schizophrenic patients. Am J Psychiatry 152:1724–1729
Yasuhara T, Shingo T, Date I (2007) Glial cell line-derived neurotrophic factor (GDNF) therapy for Parkinson’s disease. Acta Med Okayama 61:51–56
Acknowledgments
This work was supported by Rede Instituto Brasileiro de Neurociência (IBN Net/Finep), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (Fapemig), Brazil.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Scalzo, P., Kümmer, A., Bretas, T.L. et al. Serum levels of brain-derived neurotrophic factor correlate with motor impairment in Parkinson’s disease. J Neurol 257, 540–545 (2010). https://doi.org/10.1007/s00415-009-5357-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-009-5357-2