Neurodegenerative Diseases

Original Paper

BDNF Serum Levels with Respect to Multidimensional Assessment in Amyotrophic Lateral Sclerosis

Tremolizzo La, b · Pellegrini A.a, b · Conti E.b · Arosio A.b · Gerardi F.c · Lunetta C.c · Magni P.d · Appollonio I.a · Ferrarese C.a, b

Author affiliations

aNeurology Unit, San Gerardo Hospital, Monza, bSchool of Medicine and Milan Center for Neuroscience (Neuro-MI), University of Milano-Bicocca, cNeuromuscular Omnicentre (NEMO), Fondazione Serena Onlus, dDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy

Keywords: Cognitive impairmentDepressionBrain-derived neurotrophic factorAmyotrophic lateral sclerosis

Related Articles for ""
Neurodegener Dis 2016;16:192-198
https://doi.org/10.1159/000441916

Log in to MyKarger to check if you already have access to this content.




Forgot your password
Sign up to MyKarger

Buy

  • FullText & PDF
  • Unlimited re-access via MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more
CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!


If you would like to redeem your KAB credit, please log in.

Save over 20% compared to the individual article price.

Learn more

Rent/Cloud

  • Rent for 48h to view
  • Buy Cloud Access for unlimited viewing via different devices
  • Synchronizing in the ReadCube Cloud
  • Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00

Select

Subscribe

  • Access to all articles of the subscribed year(s) guaranteed for 5 years
  • Unlimited re-access via Subscriber Login or MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

Subcription rates

Select
* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: March 20, 2015
Accepted: October 22, 2015
Published online: January 09, 2016
Issue release date: April 2016

Number of Print Pages: 7
Number of Figures: 4
Number of Tables: 1

ISSN: 1660-2854 (Print)
eISSN: 1660-2862 (Online)

For additional information: https://www.karger.com/NDD

Abstract

Background: The clinical presentation of amyotrophic lateral sclerosis (ALS) is characterized by high heterogeneity, the greatest part of which still remains unexplained. Objective: To assess serum levels of brain-derived neurotrophic factor (BDNF) in ALS patients, implementing a multidimensional characterization focused on four a priori chosen elements of phenotypic variability: ALS bulbar/spinal subtype, cognitive impairment, mood dysfunction and disease progression speed. Methods: Serum samples were obtained from 45 ALS outpatients (16% bulbar onset) and 22 healthy controls. Each patient underwent the Montreal Cognitive Assessment (MoCA) and the Beck Depression Inventory (BDI), and disease progression speed was estimated by calculating the decay of the ALSFRS-R score over time. Results: BDNF serum levels did not differ between patients and controls, although ∼25% lower levels characterized those patients carrying a depressive trait. Finally, BDNF serum levels were significantly lower in ALS patients expressing lower ALSFRS-R scores (r = 0.39, p < 0.01). No differences were found when considering cognitive impairment, disease progression speed and site of onset. Conclusion: BDNF serum levels might mark and possibly contribute in part to ALS phenotypic variability.

© 2016 S. Karger AG, Basel



Related Articles:

References

  1. Swinnen B, Robberecht W: The phenotypic variability of amyotrophic lateral sclerosis. Nat Rev Neurol 2014;10:661-670.
    External Resources
  2. Murphy J, Henry R: Continuum of frontal lobe impairment in amyotrophic lateral sclerosis. Arch Neurol 2007;64:530-534.
    External Resources
  3. Strong MJ, Grace GM, Freedman M, Lomen-Hoerth C, Woolley S, Goldstein LH, Murphy J, Shoesmith C, Rosenfeld J, Leigh PN, Bruijn L, Ince P, Figlewicz D: Consensus criteria for the diagnosis of frontotemporal cognitive and behavioural syndromes in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 2009;10:131-146.
    External Resources
  4. Elamin M, Phukan J, Bede P, Jordan N, Byrne S, Pender N, Hardiman O: Executive dysfunction is a negative prognostic indicator in patients with ALS without dementia. Neurology 2011;76:1263-1269.
    External Resources
  5. Kurt A, Nijboer F, Matuz T, Kübler A: Depression and anxiety in individuals with amyotrophic lateral sclerosis: epidemiology and management. CNS Drugs 2007;21:279-291.
    External Resources
  6. Kimura F, Fujimura C, Ishida S, Nakajima H, Furutama D, Uehara H, Shinoda K, Sugino M, Hanafusa T: Progression rate of ALSFRS-R at time of diagnosis predicts survival time in ALS. Neurology 2006;66:265-267.
    External Resources
  7. Pupillo E, Messina P, Logroscino G, Beghi E: Long-term survival in amyotrophic lateral sclerosis: a population-based study. Ann Neurol 2014;75:287-297.
    External Resources
  8. Chiò A, Ilardi A, Cammarosano S, Moglia C, Montuschi A, Calvo A: Neurobehavioral dysfunction in ALS has a negative effect on outcome and use of PEG and NIV. Neurology 2012;78:1085-1089.
    External Resources
  9. Pan W, Banks WA, Fasold MB, Bluth J, Kastin AJ: Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology 1998;37:1553-1561.
    External Resources
  10. Sartorius A, Hellweg R, Litzke J, Vogt M, Dormann C, Vollmayr B, Danker-Hopfe H, Gass P: Correlations and discrepancies between serum and brain tissue levels of neurotrophins after electroconvulsive treatment in rats. Pharmacopsychiatry 2009;42:270-276.
    External Resources
  11. Henderson CE, Camu W, Mettling C, Gouin A, Poulsen K, Karihaloo M, Rullamas J, Evans T, McMahon SB, Armanini MP: Neurotrophins promote motor neuron survival and are present in embryonic limb bud. Nature 1993;363:266-270.
    External Resources
  12. Sendtner M, Holtmann B, Kolbeck R, Thoenen H, Barde YA: Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section. Nature 1992;360:757-759.
    External Resources
  13. Koliatsos VE, Clatterbuck RE, Winslow JW, Cayouette MH, Price DL: Evidence that brain-derived neurotrophic factor is a trophic factor for motor neurons in vivo. Neuron 1993;10:359-367.
    External Resources
  14. Novikova L, Novikov L, Kellerth JO: Effects of neurotransplants and BDNF on the survival and regeneration of injured adult spinal motoneurons. Eur J Neurosci 1997;9:2774-2777.
    External Resources
  15. Ikeda K, Klinkosz B, Greene T, Cedarbaum JM, Wong V, Lindsay RM, Mitsumoto H: Effects of brain-derived neurotrophic factor on motor dysfunction in wobbler mouse motor neuron disease. Ann Neurol 1995;37:505-511.
    External Resources
  16. Mitsumoto H, Ikeda K, Klinkosz B, Cedarbaum JM, Wong V, Lindsay RM: Arrest of motor neuron disease in wobbler mice cotreated with CNTF and BDNF. Science 1994;265:1107-1110.
    External Resources
  17. Ochs G, Penn RD, York M, Giess R, Beck M, Tonn J, Haigh J, Malta E, Traub M, Sendtner M, Toyka KV: A phase I/II trial of recombinant methionyl human brain derived neurotrophic factor administered by intrathecal infusion to patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2000;1:201-206.
    External Resources
  18. A controlled trial of recombinant methionyl human BDNF in ALS: The BDNF Study Group (Phase III). Neurology 1999;52:1427-1433.
    External Resources
  19. Duberley RM, Johnson IP, Anand P, Leigh PN, Cairns NJ: Immunocytochemical studies of neurotrophins in cerebral motor cortex in amyotrophic lateral sclerosis. Brain Res 1997;763:259-263.
    External Resources
  20. Kawamoto Y, Nakamura S, Akiguchi I, Kimura J: Immunohistochemical localization of brain-derived neurotrophic factor in the spinal cords of amyotrophic lateral sclerosis and non-amyotrophic lateral sclerosis patients. J Neuropathol Exp Neurol 1998;57:822-830.
    External Resources
  21. Nishio T, Sunohara N, Furukawa S: Neutrophin switching in spinal motoneurons of amyotrophic lateral sclerosis. Neuroreport 1998;9:1661-1665.
    External Resources
  22. Grundström E, Lindholm D, Johansson A, Blennow K, Askmark H: GDNF but not BDNF is increased in cerebrospinal fluid in amyotrophic lateral sclerosis. Neuroreport 2000;11:1781-1783.
    External Resources
  23. Grundström E, Askmark H, Lindeberg J, Nygren I, Ebendal T, Aquilonius SM: Increased expression of glial cell line-derived neurotrophic factor mRNA in muscle biopsies from patients with amyotrophic lateral sclerosis. J Neurol Sci 1999;162:169-173.
    External Resources
  24. Küst BM, Copray JCVM, Brouwer N, Troost D, Boddeke HWGM: Elevated levels of neurotrophins in human biceps brachii tissue of amyotrophic lateral sclerosis. Exp Neurol 2002;177:419-427.
    External Resources
  25. Angelucci F, Oliviero A, Pilato F, Saturno E, Dileone M, Versace V, Musumeci G, Batocchi AP, Tonali PA, Di Lazzaro V: Transcranial magnetic stimulation and BDNF plasma levels in amyotrophic lateral sclerosis. Neuroreport 2004;15:717-720.
    External Resources
  26. Iłzecka J, Stelmasiak Z: Brain-derived neurotrophic factor is not altered in the serum and cerebrospinal fluid of amyotrophic lateral sclerosis patients. Neurol Sci 2002;22:473-474.
    External Resources
  27. Teixeira A, Barbosa I: Circulating levels of brain-derived neurotrophic factor: correlation with mood, cognition and motor function. Biomark Med 2010;871-887.
    External Resources
  28. Ventriglia M, Zanardini R, Bonomini C, Zanetti O, Volpe D, Pasqualetti P, Gennarelli M, Bocchio-Chiavetto L: Serum brain-derived neurotrophic factor levels in different neurological diseases. Biomed Res Int 2013;2013:901082.
    External Resources
  29. Weinstein G, Beiser AS, Choi SH, Preis SR, Chen TC, Vorgas D, Au R, Pikula A, Wolf PA, DeStefano AL, Vasan RS, Seshadri S: Serum brain-derived neurotrophic factor and the risk for dementia: the Framingham Heart Study. JAMA Neurol 2014;71:55-61.
    External Resources
  30. Zuccato C, Marullo M, Vitali B, Tarditi A, Mariotti C, Valenza M, Lahiri N, Wild EJ, Sassone J, Ciammola A, Bachoud-Lèvi AC, Tabrizi SJ, Di Donato S, Cattaneo E: Brain-derived neurotrophic factor in patients with Huntington's disease. PLoS One 2011;6: e22966.
    External Resources
  31. Trajkovska V, Marcussen AB, Vinberg M, Hartvig P, Aznar S, Knudsen GM: Measurements of brain-derived neurotrophic factor: methodological aspects and demographical data. Brain Res Bull 2007;73:143-149.
    External Resources
  32. Ziegenhorn AA, Schulte-Herbrüggen O, Danker-Hopfe H, Malbranc M, Hartung HD, Anders D, Lang UE, Steinhagen-Thiessen E, Schaub RT, Hellweg R: Serum neurotrophins - a study on the time course and influencing factors in a large oldage sample. Neurobiol Aging 2007;28:1436-1445.
    External Resources
  33. Brooks BR, Miller RG, Swash M, Munsat TL; World Federation of Neurology Research Group on Motor Neuron Diseases: El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2000;1:293-299.
    External Resources
  34. Tremolizzo L, Ferrarese C, Appollonio I: Exploring limits of neuropsychological screening in ALS: the FAB problem. Amyotroph Lateral Scler Frontotemporal Degener 2013;14:157-158.
    External Resources
  35. Osborne RA, Sekhon R, Johnston W, Kalra S: Screening for frontal lobe and general cognitive impairment in patients with amyotrophic lateral sclerosis. J Neurol Sci 2014;336:191-196.
    External Resources
  36. Laiacona M, Inzaghi MG, De Tanti A, Capitani E: Wisconsin card sorting test: a new global score, with Italian norms, and its relationship with the Weigl sorting test. Neurol Sci 2000;21:279-291.
    External Resources
  37. Pagnini F, Lunetta C, Rossi G, Banfi P, Gorni K, Cellotto N, Castelnuovo G, Molinari E, Corbo M: Existential well-being and spirituality of individuals with amyotrophic lateral sclerosis is related to psychological well-being of their caregivers. Amyotroph Lateral Scler 2011;12:105-108.
    External Resources
  38. Tremolizzo L, Susani E, Lunetta C, Corbo M, Ferrarese C, Appollonio I: Primitive reflexes in amyotrophic lateral sclerosis: prevalence and correlates. J Neurol 2014;261:1196-1202.
    External Resources
  39. Colombo E, Bedogni F, Lorenzetti I, Landsberger N, Previtali SC, Farina C: Autocrine and immune cell-derived BDNF in human skeletal muscle: implications for myogenesis and tissue regeneration. J Pathol 2013;231:190-198.
    External Resources
  40. Fujimura H, Altar CA, Chen R, Nakamura T, Nakahashi T, Kambayashi J, Sun B, Tandon NN: Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation. Thromb Haemost 2002;87:728-734.
    External Resources
  41. Chaldakov GN, Fiore M, Hristova MG, Aloe L: Metabotrophic potential of neurotrophins: implication in obesity and related diseases? Med Sci Monit 2003;9:HY19-HY21.
    External Resources
  42. He Y-Y, Zhang X-Y, Yung W-H, Zhu J-N, Wang J-J: Role of BDNF in central motor structures and motor diseases. Mol Neurobiol 2013;48:783-793.
    External Resources
  43. Petoukhov E, Fernando S, Mills F, Shivji F, Hunter D, Krieger C, Silverman MA, Bamji SX: Activity-dependent secretion of progranulin from synapses. J Cell Sci 2013;126:5412-5421.
    External Resources
  44. Sleegers K, Brouwers N, Maurer-Stroh S, van Es MA, Van Damme P, van Vught PWJ, van der Zee J, Serneels S, De Pooter T, Van den Broeck M, Cruts M, Schymkowitz J, De Jonghe P, Rousseau F, van den Berg LH, Robberecht W, Van Broeckhoven C: Progranulin genetic variability contributes to amyotrophic lateral sclerosis. Neurology 2008;71:253-259.
    External Resources
  45. de Azevedo Cardoso T, Mondin TC, Wiener CD, Marques MB, Fucolo BDÁ, Pinheiro RT, de Souza LDM, da Silva RA, Jansen K, Oses JP: Neurotrophic factors, clinical features and gender differences in depression. Neurochem Res 2014;1571-1578.
    External Resources
  46. Molendijk ML, Spinhoven P, Polak M, Bus BA, Penninx BW, Elzinga BM: Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (n = 9,484). Mol Psychiatry 2014;19:791-800.
    External Resources
  47. Kimpton J: The brain derived neurotrophic factor and influences of stress in depression. Psychiatr Danub 2012;24(suppl 1):S169-S171.
    External Resources
  48. Pluchino N, Russo M, Santoro a N, Litta P, Cela V, Genazzani a R: Steroid hormones and BDNF. Neuroscience 2013;239:271-279.
    External Resources
  49. Phukan J, Elamin M, Bede P, Jordan N, Gallagher L, Byrne S, Lynch C, Pender N, Hardiman O: The syndrome of cognitive impairment in amyotrophic lateral sclerosis: a population-based study. J Neurol Neurosurg Psychiatry 2012;83:102-108.
    External Resources
  50. Conti S, Bonazzi S, Laiacona M, Masina M, Coralli MV: Montreal Cognitive Assessment (MoCA)-Italian version: regression based norms and equivalent scores. Neurol Sci 2015;36:209-214.
    External Resources
  51. Woolley SC, York MK, Moore DH, Strutt AM, Murphy J, Schulz PE, Katz JS: Detecting frontotemporal dysfunction in ALS: utility of the ALS Cognitive Behavioral Screen (ALS-CBS). Amyotroph Lateral Scler 2010;11:303-311.
    External Resources
  52. Murphy J, Ahmed F, Lomen-Hoerth C: The UCSF screening exam effectively screens cognitive and behavioral impairment in patients with ALS. Amyotroph Lateral Scler Frontotemporal Degener 2014;1-7.
    External Resources
  53. Zhao W, Beers DR, Appel SH: Immune-mediated mechanisms in the pathoprogression of amyotrophic lateral sclerosis. J Neuroimmune Pharmacol 2013;8:888-899.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: March 20, 2015
Accepted: October 22, 2015
Published online: January 09, 2016
Issue release date: April 2016

Number of Print Pages: 7
Number of Figures: 4
Number of Tables: 1

ISSN: 1660-2854 (Print)
eISSN: 1660-2862 (Online)

For additional information: https://www.karger.com/NDD

Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Article Tools
Article Details

2016, Vol.16, No. 3-4

April 2016

Article

Recommend This
TOP