Highlights
- •pwMS presented lower BDNF serum concentration than healthy people.
- •BDNF serum concentration was not related to clinical/gait outcomes in pwMS and healthy people.
- •BDNF does not play an essential role in gait parameters.
Abstract
Background
It has been suggested that the protein Brain-derived Neurotrophic Factor (BDNF) plays
a neuroprotective role in people with multiple sclerosis (pwMS). Also, BDNF seems
to play a role in cognition performance. In the same line, gait in pwMS requires a
higher cognitive resource, mainly during complex walking. Thus, maybe BDNF could be
related to gait in pwMS.
Objective
To investigate the relationship between BDNF and gait spatial-temporal parameters
during unobstructed and obstructed conditions and the Timed Up and Go (TUG) in pwMS
and healthy controls (HC).
Methods
The study included 20 pwMS (11F/9M, 33.1±7.5 years, Expanded Disability Status Scale-
EDSS 2.2±1.2) and 18 HC (13F/5M, 35.5±5.9 years). Both groups performed 20 gait attempts
in two conditions: unobstructed walking (10 trials) and avoiding an obstacle. The
obstacle was 15 cm in height and made of foam material. The BDNF serum concentration
was collected with participants in fasting and completed before the clinical, gait,
and mobility assessments. Clinical variables included the Symbol Digit Modality Test
(SDMT), the Fatigue Severity Scale (FSS), and the International Physical Activity
Questionnaire (IPAQ- short version). Associations between BDNF and spatial-temporal
gait parameters, clinical variables, and TUG were determined by Pearson/Spearman correlations
with Bonferroni's correction being applied (p<0.0013). Gait was compared by a two-way,
repeated-measures ANOVA (group and condition) to characterize our cohort.
Results
Reduced BDNF was observed for pwMS (41.66±4.45 ng/ml) in comparison with HC (61.67±7.07,
p<0.001). However, although some correlations presented a moderate correlation between
BDNF with gait variables, the correlations didn't reach a significant p-value after
Bonferroni's correction. Lastly, pwMS presented shorter step length and slower step
velocity for both gait conditions, with more evidence for obstacle conditions. Only
pwMS changed gait behavior from unobstructed walking to obstacle avoidance conditions
(i.e., reduced step length and velocity and increased step duration).
Conclusion
BDNF is not related to either clinical (i.e., EDSS, SDMT, FSS, or IPAQ) or gait parameters
in pwMS and HC, even in a condition involving higher cognitive demand. These results
may suggest that BDNF does not play a role in these parameters' performance.
Keywords
Abbreviations:
BDNF (Brain-Derived Neurotrophic Factor), pwMS (People with Multiple Sclerosis), MS (Multiple Sclerosis), CNS (Central Nervous System), EDSS (expanded disability status scale), TUG (Timed up and Go), SDMT (Symbol digit modality test), FSS (Fatigue Severity Scale), IPAQ (International Physical Activity Questionnaire), METs (Metabolic Equivalent of Task units), ELISA (Enzyme-Linked Immunosorbent Assay), MMSE (Mini-Mental State Exam), PDDS (Patient Determined Disease Steps)To read this article in full you will need to make a payment
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References
- BDNF function in health and disease poster.Nat. Rev. Neurosci. 2014; : 4866
- Low and dysregulated BDNF secretion from immune cells of MS patients is related to reduced neuroprotection.J. Neuroimmunol. 2008; 195: 186-193https://doi.org/10.1016/j.jneuroim.2008.01.010
- Serum brain-derived neurotrophic factor response to aerobic exercise in multiple sclerosis.J. Neurol. Sci. 2008; 269: 85-91https://doi.org/10.1016/j.jns.2007.12.030
- Sex differences in brain-derived neurotrophic factor signaling and functions.J. Neurosci. Res. 2017; 95: 328-335https://doi.org/10.1002/jnr.23863
- Frontal brain activation changes due to dual-tasking under partial body weight support conditions in older adults with multiple sclerosis.J. NeuroEng. Rehab. 2017; 14: 1-10https://doi.org/10.1186/s12984-017-0280-8
- Gait deficits in people with multiple sclerosis: A systematic review and meta-analysis.Gait Posture. 2017; 51: 25-35https://doi.org/10.1016/j.gaitpost.2016.09.026
- Serum levels of brain-derived neurotrophic factor correlate with the number of T2 MRI lesions in multiple sclerosis.Braz. J. Med. Biol. Res. 2012; 45: 68-71https://doi.org/10.1590/S0100-879X2011007500165
- Multiple correlations and Bonferroni's correction.Biol. Psychiatry. 1998; 44: 775-777https://doi.org/10.1016/S0006-3223(98)00043-2
- Serum BDNF levels are not reliable correlates of neurodegeneration in MS patients.Multiple Sclerosis Rel. Disorders. 2015; 4: 65-66https://doi.org/10.1016/j.msard.2014.11.003
- Validation of the Brazilian version of the patient-determined disease steps scale in persons with multiple sclerosis.Multiple Sclerosis Rel. Disorders. 2019; 30: 208-214https://doi.org/10.1016/j.msard.2019.02.022
- Fitness Shifts the Balance of BDNF and IL-6 from Inflammation to Repair among People with Progressive Multiple Sclerosis.Biomolecules. 2021; 11: 504https://doi.org/10.3390/biom11040504
- Effects of exercise training on neurotrophic factors and subsequent neuroprotection in persons with multiple sclerosis—a systematic review and meta-analysis.Brain Sci. 2021; 11https://doi.org/10.3390/brainsci11111499
- Regionally specific effects of BDNF on oligodendrocytes.Dev. Neurosci. 2003; 25: 116-126https://doi.org/10.1159/000072261
- “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician.J. Psychiatr. Res. 1975; 12: 189-198https://doi.org/10.1016/0022-3956(75)90026-6
- Increased plasma levels of brain derived neurotrophic factor (BDNF) after multiple sclerosis relapse.Neurosci. Lett. 2009; 460: 130-132https://doi.org/10.1016/j.neulet.2009.05.057
- BDNF and Tau as biomarkers of severity in multiple sclerosis.Biomark. Med. 2018; 12: 717-726https://doi.org/10.2217/bmm-2017-0374
- Immune-cell BDNF expression in treatment-naïve relapsing-remitting multiple sclerosis patients and following one year of immunomodulation therapy.Neurol. Neurochir. Pol. 2018; : 1-7https://doi.org/10.1016/j.pjnns.2018.03.006
- Gait characteristics according to pyramidal, sensory and cerebellar EDSS subcategories in people with multiple sclerosis.J. Neurol. 2016; 263: 1796-1801https://doi.org/10.1007/s00415-016-8200-6
- Blood BDNF concentrations reflect brain-tissue BDNF levels across species.Int. J. Neuropsychopharmacolog. 2011; 14: 347-353https://doi.org/10.1017/S1461145710000738
- The Fatigue Severity Scale.Arch. Neurol. 1989; 46: 1121https://doi.org/10.1001/archneur.1989.00520460115022
- Neural Plasticity in Multiple Sclerosis: The Functional and Molecular Background.Neural Plasticity 2015. 2015; https://doi.org/10.1155/2015/307175
- Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS).Neurology. 1983; 33: 1444-1452https://doi.org/10.1212/WNL.33.11.1444
- Impact of Walking Impairment in Multiple Sclerosis.Patient. 2011; 4: 189-201https://doi.org/10.2165/11591150-000000000-00000
- BDNF mediates improvements in executive function following a 1-year exercise intervention.Front. Hum. Neurosci. 2014; 8: 1-12https://doi.org/10.3389/fnhum.2014.00985
- The Role of the Frontal Lobe in Complex Walking among Patients with Parkinson's Disease and Healthy Older Adults: An fNIRS Study.Neurorehabil. Neural Repair. 2016; 30: 963-971https://doi.org/10.1177/1545968316650426
- Altered brain activation in complex walking conditions in patients with Parkinson's disease.Parkinsonism Relat. Disord. 2016; 25: 91-96
- Questionário Internacional De Atividade Física (Ipaq): Estupo De Validade E Reprodutibilidade No Brasil.Revista Brasileira de Atividade Física & Saúde. 2012; 6: 5-18https://doi.org/10.12820/rbafs.v.6n2p5-18
- Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the Diagnosis of Multiple Sclerosis.Ann. Neurol. 2001; 50: 121-127https://doi.org/10.1002/ana.1032
- Increased serum brain-derived neurotrophic factor in multiple sclerosis patients on interferon-b and its impact on functional abilities.Neurologist. 2015; 20: 57-60https://doi.org/10.1097/NRL.0000000000000053
- Levels of brain-derived neurotrophic factor in patients with multiple sclerosis.Ann. Clin. Transl. Neurol. 2020; 7: 2251-2261https://doi.org/10.1002/acn3.51215
- Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain.Brain Res. 1996; 726: 49-56https://doi.org/10.1016/0006-8993(96)00273-9
- Serum level of brain-derived neurotrophic factor in patients with relapsing–remitting multiple sclerosis: a potential biomarker for disease activity.Egyptian J. Neurol. Psychiatry Neurosurg. 2021; 57https://doi.org/10.1186/s41983-021-00296-2
- Transport of brain-derived neurotrophic factor across the blood-brain barrier.Neuropharmacology. 1998; 37: 1553-1561https://doi.org/10.1016/S0028-3908(98)00141-5
- Correlations between peripheral blood mononuclear cell production of BDNF, TNF-alpha, IL-6, IL-10 and cognitive performances in multiple sclerosis patients.J. Neurosci. Res. 2010; 88: 1106-1112https://doi.org/10.1002/jnr.22276
- Are static and functional balance abilities related in individuals with Multiple Sclerosis?.Multiple Sclerosis Rel. Disorders. 2017; 15: 1-6https://doi.org/10.1016/j.msard.2017.04.002
- Brain-derived neurotrophic factor (BDNF) as a potential mechanism of the effects of acute exercise on cognitive performance.J. Sport Health Sci. 2015; 4: 14-23https://doi.org/10.1016/j.jshs.2014.11.001
- Spatial and temporal characteristics of Gait as outcome measures in multiple sclerosis (EDSS 0 to 6.5).J. NeuroEng. Rehab. 2015; 12: 1-7https://doi.org/10.1186/s12984-015-0001-0
- Early cognitive impairment along with decreased stress-induced BDNF in male and female patients with newly diagnosed multiple sclerosis.J. Neuroimmunol. 2017; 302: 34-40https://doi.org/10.1016/j.jneuroim.2016.11.007
- Cortical activity and gait parameter characteristics in people with multiple sclerosis during unobstructed gait and obstacle avoidance.Gait Posture. 2021; 86: 226-232https://doi.org/10.1016/j.gaitpost.2021.03.026
- Brain-derived neurotrophic factor in patients with multiple sclerosis.J. Neuroimmunol. 2002; 132: 180-188https://doi.org/10.1016/S0165-5728(02)00319-3
- Correlation coefficients: Appropriate use and interpretation.Anesth. Analg. 2018; 126: 1763-1768https://doi.org/10.1213/ANE.0000000000002864
- Validity of the Timed Up and Go Test as a Measure of Functional Mobility in Persons with Multiple Sclerosis.Arch. Phys. Med. Rehabil. 2016; 97: 1072-1077https://doi.org/10.1016/j.apmr.2015.12.031
- Endurance training enhances BDNF release from the human brain.Am. J. Physiol. Regulatory Integrat. Compar. Physiol. 2010; 298: 372-377https://doi.org/10.1152/ajpregu.00525.2009
Smith, A., 1982. Symbol digit modalities test: Manual. Western Psychological Services.
- Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria.Lancet Neurol. 2018; 17: 162-173https://doi.org/10.1016/S1474-4422(17)30470-2
- Multiple sclerosis.Lancet North Am. Ed. 2018; 391: 1622-1636https://doi.org/10.1016/S0140-6736(18)30481-1
- Altered serum content of brain-derived neurotrophic factor isoforms in multiple sclerosis.J. Neurol. Sci. 2012; 320: 161-165https://doi.org/10.1016/j.jns.2012.07.016
- Brain-derived neurotrophic factor levels under chronic natalizumab treatment in multiple sclerosis. A preliminary report.Neurol. Neurochir. Pol. 2017; 51: 221-226https://doi.org/10.1016/j.pjnns.2017.03.002
Article info
Publication history
Published online: July 21, 2022
Accepted:
July 17,
2022
Received in revised form:
March 25,
2022
Received:
July 8,
2021
Identification
Copyright
© 2022 Elsevier B.V. All rights reserved.
