title: Intensive Rehabilitation Enhances Lymphocyte BDNF-TrkB Signaling in Patients With Parkinson's Disease.
abstract: 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.
authors.affiliation: Sophie Davis School for Biomedical Education at CCNY, CUNY, New York, NY, USA The Graduate Center, CUNY, New York, NY, USA.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Fontanesi
authors.affiliation: Sophie Davis School for Biomedical Education at CCNY, CUNY, New York, NY, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Kvint
authors.affiliation: "Moriggia Pelascini" Hospital, Gravedona ed Uniti, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Frazzitta
authors.affiliation: "Moriggia Pelascini" Hospital, Gravedona ed Uniti, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Bera
authors.affiliation: "Moriggia Pelascini" Hospital, Gravedona ed Uniti, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Ferrazzoli
authors.affiliation: The Fresco Institute for Parkinson's & Movement Disorders, NYU-Langone School of Medicine, New York, NY, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Di Rocco
authors.affiliation: Sophie Davis School for Biomedical Education at CCNY, CUNY, New York, NY, USA.
authors.forename: Heike
authors.initials: H
authors.lastname: Rebholz
authors.affiliation: Sophie Davis School for Biomedical Education at CCNY, CUNY, New York, NY, USA.
authors.forename: Eitan
authors.initials: E
authors.lastname: Friedman
authors.affiliation: Istituti Clinici di Perfezionamento, Milano, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Pezzoli
authors.affiliation: The Fresco Institute for Parkinson's & Movement Disorders, NYU-Langone School of Medicine, New York, NY, USA IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Department of Neuroscience, University of Messina, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Quartarone
authors.affiliation: Sophie Davis School for Biomedical Education at CCNY, CUNY, New York, NY, USA.
authors.forename: Hoau-Yan
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Sophie Davis School for Biomedical Education at CCNY, CUNY, New York, NY, USA The Fresco Institute for Parkinson's & Movement Disorders, NYU-Langone School of Medicine, New York, NY, USA lice.mg79@gmail.com.
authors.forename: M Felice
authors.initials: MF
authors.lastname: Ghilardi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D015444:Exercise; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009788:Occupational Therapy; D010300:Parkinson Disease / Q000473:pathology / Q000534:rehabilitation*; D026741:Physical Therapy Modalities; D020813:Receptor, trkB / Q000378:metabolism*; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB
keywords: LTP; human; immune system; plasticity