Intensive Rehabilitation Enhances Lymphocyte BDNF-TrkB Signaling in Patients With Parkinson’s Disease
Open accessAbstract
Background In a combined animal and human study, we have previously found that a 5-day treatment that enhances cortical plasticity also facilitates brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling and increases activated TrkB and N-methyl-d-aspartate receptor (NMDAR) association in both the cortex and the peripheral lymphocytes. Patients with Parkinson's disease (PD), in general, show decreased cortical plasticity, as demonstrated by electrophysiological and behavioral studies. Here, we test the hypothesis that an exercise program that improves motor function and seems to slow down symptom progression can enhance BDNF-TrkB signaling in lymphocytes. Methods A total of 16 patients with PD underwent a 4-week multidisciplinary intensive rehabilitation treatment (MIRT), which included aerobic training and physical and occupational therapy. Blood was collected before and after 2 and 4 weeks of MIRT. Lymphocytes were isolated to examine BDNF-TrkB signaling induced by incubation with recombinant human BDNF. TrkB signaling complexes, extracellular-signal-regulated kinase-2 and protein-kinase-B were immunoprecipitated; the content of immunocomplexes was determined by Western blotting. Results After MIRT, all patients showed improvement in motor function. TrkB interaction with NMDAR and BDNF-TrkB signaling increased in peripheral lymphocytes at receptor, intracellular mediator, and downstream levels. The decrements in Unified Parkinson's Disease Rating Scale II (UPDRSII) and total scores were significantly correlated with the increases in TrkB signaling at receptor, intracellular mediator, and NMDAR interaction levels. Conclusions The significant correlation between reduced UPDRS scores and the changes in lymphocyte activity suggest that enhanced BDNF-TrkB signaling in lymphocyte and reduced severity of PD symptoms may be related.
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Exercise may activate extracellular signals known to inhibit GSK-3, including BDNF.
“Exercise may activate some extracellular signals that are known to inhibit GSK-3, including BDNF [180,206].”
From BDNF as a Promising Therapeutic Agent in Parkinson’s Disease (2020) · cites this paper as [180]
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- Authors
- Fontanesi, C., Kvint, S., Frazzitta, G., Bera, R., Ferrazzoli, D., Di Rocco, A., Rebholz, H., Friedman, E., Pezzoli, G., Quartarone, A., Wang, H.-Y., & Ghilardi, M. F.
- Affiliations
- The Graduate Center, CUNY (US)
- City College of New York (US)
- Moriggia Pelascini Hospital (IT)
- The Fresco Institute for Parkinson’s & Movement Disorders, NYU-Langone School of Medicine, New York, NY, USA
- Istituti Clinici di Perfezionamento (IT)
- University of Messina (IT)
- Corresponding author
- Ghilardi, M. Felice
- ORCID
- Venue
- Neurorehabilitation and neural repair
- Publisher
- SAGE Publications
- Published
- 2015-08-07
- Volume
- 30
- Issue
- 5
- Pages
- 411-418
- ISSN
- 0888-4390 (ISSN-L)
- 1545-9683
- 1552-6844
- PMC
- PMC4744811
- OpenAlex
- W2122687322
- Cited by
- 54
- References
- 31
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 5 · 2021: 6 · 2020: 12 · 2019: 2 · 2018: 8 · 2017: 3 · 2016: 1
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurorehabilitation and neural repair (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS054864)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- Parkinson's disease, BDNF/TrkB signaling, lymphocytes, intensive rehabilitation, aerobic exercise, NMDA receptor, cortical plasticity, motor function, UPDRS scores, peripheral blood cells
- MeSH terms
- Aged, Aged, 80 and over, Female, Follow-Up Studies, Gene Expression Regulation, Humans, Lymphocytes, Male, Middle Aged, Occupational Therapy, Parkinson Disease, Severity of Illness Index, Signal Transduction, Exercise, Brain-Derived Neurotrophic Factor, Receptor, trkB, Physical Therapy Modalities
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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