HAC (Russian)
RSCI (Russian)
Ulrichsweb (Ulrich’s Periodicals Directory)
Scientific Indexing Services

Brain-derived neurotrophic factor as an indicator of central nervous system diseases

DOI: https://doi.org/10.29296/25877305-2021-04-01

Yu. Zykova(1); L. Evert(2), MD; T. Potupchik(3), Candidate of Medical Sciences (1)OOO «Medicine
of Computer Technologies» Medical and Diagnostic Clinic, Krasnoyarsk (2)Research Institute for Medical
Problems of the North, Federal Research Center “Krasnoyarsk Research Center, Siberian Branch, Russian
Academy of Sciences (3)Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health
of Russia

The paper reviews the literature on the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of many diseases of the central nervous system. It presents data of the studies showing a correlation between BDNF deficiency in the brain and blood tissues and neurodegenerative diseases, such as Alzheimer’s, Huntington’s, Parkinson’s diseases, hypoxia, headaches and migraines, and psychoemotional disorders. It is shown that BDNF can serve as a marker for predicting the course of diseases and evaluating the efficiency of treatment.

brain-derived neurotrophic factor
neurodegenerative diseases
psychoemotional disorders

  1. Astrahanova T.A., Urazov M.D., Usenko A.V. i dr. BDNF-oposredovannaja reguljatsija funktsional'nogo sostojanija mitohondrij kletok golovnogo mozga v uslovijah gipoksii. Sovremennye tehnologii v meditsine. 2018; 10 (3): 88–94 [Astrakhanova T.A., Urazov M.D., Usenko A.V. et al. BDNF-mediated regulation of the brain mitochondria functional state in hypoxia. Modern technologies in medicine. 2018; 10 (3): 88–94 (in Russ.)]. DOI: 10.17691/stm2018.10.3.10
  2. Belousova N.P., Gromova O.A., Pepeljaev E.G. i dr. Vzaimosvjaz' kognitivnyh narushenij i urovnja BDNF u lits molodogo vozrasta. Meditsina v Kuzbasse. 2017; 16 (4): 39–43 [Belousova N.P., Gromova O.A., Pepelyaev E.G. et al. The relationship between cognitive impairment and the level of BDNF in young people. Medicine in Kuzbass. 2017; 16 (4): 39–43 (in Russ.)].
  3. Rudnitskaja E.A., Kolosova N.G., Stefanova N.A. Nejrotroficheskoe obespechenie golovnogo mozga v ontogeneze i pri razvitii nejrodegenerativnyh zabolevanij. Vestnik Moskovskogo Universiteta. Serija 16: Biologija. 2016; 4: 72–82 [Rudnitskaya E.A., Kolosova N.G., Stefanova N.A. Brain neurotrophic supplementation in onthogenesis and during development of neurodegenerative diseases. Vestnik Moskovskogo Universiteta. Seriya 16. Biologiya. 2016; 4: 72–82 (in Russ.)].
  4. Tjan K.V., Kalinskij P.P., Rakitova A.V. Trevozhno-depressivnaja simptomatika i uroven' nejrotroficheskogo faktora golovnogo mozga u patsientov s golovnoj bol'ju naprjazhenija. Permskij meditsinskij zhurnal. 2017; 34 (6): 34–9 [Tyan K.V., Kalinsky P.P., Rakitova A.V. Anxious-depressive symptomatology and brain-derived neurotrophic factor level in patients with tension headache. Perm Med J. 2017; 34 (6): 34–9 (in Russ.)]. DOI: 10.17816/pmj34634-39
  5. Evert L.S., Potupchik T.V., Reusheva S.V. i dr. Uroven' mozgovogo nejrotroficheskogo faktora BDNF u podrostkov s displaziej soedinitel'noj tkani i razlichnymi psihosomaticheskimi sindromami. Sovremennye problemy nauki i obrazovanija. 2018; 5: 61 [Evert L.S., Potupchik T.V., Reusheva S.V. et al. The level of brain neurotrophic factor BDNF in adolescents with connective tissue dysplasia and various psychosomatic syndromes. Modern problems of science and education. 2018; 5: 61 (in Russ.)]. URL: http://science-education.ru/ru/article/view?id=28072
  6. Anderson M.A., Burda J.E., Ren Y. et al. Astrocyte scar formation aids central nervous system axon regeneration. Nature. 2016; 532 (7598): 195–200. DOI: 10.1038/nature17623
  7. Badrlou E., Ghafouri-Fard S., Omrani M.D. et al. Expression of BDNF-Associated lncRNAs in Treatment-Resistant Schizophrenia Patients. Mol Neurosci. 2021; 5. Online ahead of print. DOI: 10.1007/s12031-020-01772-9
  8. Bawari S., Sandro T., Archana A. et al. Targeting BDNF signaling by natural products: novel synaptic repair therapeutics for neurodegeneration and behavior disorders. Pharmacol Res. 2019; 148: 104458. DOI: 10.1016/j.phrs.2019.104458.
  9. Beeri M.S., Sonnen J. Brain BDNF expression as a biomarker for cognitive reserve against Alzheimer disease progression. Neurology. 2016; 86 (8): 702–3. DOI: 10.1212/WNL.0000000000002389
  10. Blanco-Suárez E., Caldwell A.L., Allen N.J. Role of astrocyte-synapse interactions in CNS disorders. J Physiol. 2017; 595 (6): 1903–16. DOI: 10.1113/JP270988
  11. Blandini F., Rinaldi L., Tassorelli C. et al. Peripheral levels of BDNF and NGF in primary headaches. Cephalalgia. 2006; 26 (2): 136–42. DOI: 10.1111/j.1468-2982.2005.01006.x
  12. Boschen K.E., Klintsova A.Y. Neurotrophins in the brain: interaction with alcohol exposure during development. Vitamins and hormones. 2017; 104: 197–242. DOI: 10.1016/bs.vh.2016.10.008
  13. Budni J., Bellettini-Santos T., Mina F. et al. The involvement of BDNF, NGF and GDNF in aging and Alzheimer’s disease. Aging Dis. 2015; 6 (5): 331–41. DOI: 10.14336/AD.2015.0825
  14. Chan A., Yan J., Csurhes P. et al. Circulating brain derived neurotrophic factor (BDNF) and frequency of BDNF positive T cells in peripheral blood in human ischemic stroke: effect on outcome. J Neuroimmunol. 2015; 286: 42–7. DOI: 10.1016/j.jneuroim.2015.06.013
  15. De Almeida Claudino F.C., Gonçalves L., Felipe Barreto Schuch F.B. et al. The Effects of Individual Psychotherapy in BDNF Levels of Patients With Mental Disorders: A Systematic Review. Front Psychiatry. 2020; 11: 445. DOI: 10.3389/fpsyt.2020.00445
  16. Devi L., Ohno M. TrkB reduction exacerbates Alzheimer’s disease-like signaling aberrations and memory deficits without affecting beta-amyloidosis in 5XFAD mice. Transl Psychiatry. 2015; 5 (5): e562. DOI: 10.1038/tp.2015.55
  17. Eyileten C., Kaplon-Cieslicka A., Mirowska-Guzel D. et al. Antidiabetic effect of brain-derived neurotrophic factor and its association with inflammation in type 2 diabetes mellitus. J Diabetes Res. 2017; 2017: 1–14. DOI: 10.1155/2017/2823671
  18. Ferreira R.N., de Miranda A.S., Rocha N.P. et al. Neurotrophic factors in Parkinson’s disease: what have we learned from pre-clinical and clinical studies? Curr Med Chem. 2018; 25: 3682–702. DOI: 10.2174/0929867325666180313101536
  19. Fischer M., Wille G., Klien S. et al. Brain-derived neurotrophic factor in primary headaches. J Headache Pain. 2012; 13 (6): 469–75. DOI: 10.1007/s10194-012-0454-5
  20. Gandolfi M., Smania N., Vella A. et al. Assessed and Emerging Biomarkers in Stroke and Training-Mediated Stroke Recovery: State of the Art. Neural Plast. 2017; 2017: 1389475. DOI: 10.1155/2017/1389475
  21. Geisel O., Banas R., Schneider M. et al. Serum levels of brain-derived neurotrophic factor in patients with internet use disorder. Psychiatry Res. 2013; 209 (3): 525–8. DOI: 10.1016/j.psychres.2012.12.020.
  22. Gorshkov K., Aguisanda F., Thorne N. et al. Astrocytes as targets for drug discovery. Drug Discov Today. 2018; 23 (3): 673–80. DOI: 10.1016/j.drudis.2018.01.011
  23. Hing B., Sathyaputri L., Potash J.B. A comprehensive review of genetic and epigenetic mechanisms that regulate BDNF expression and function with relevance to major depressive disorder. Am J Med Genet B Neuropsychiatr Genet. 2018; 177 (2): 143–67. DOI: 10.1002/ajmg.b.32616
  24. Hwang K.S., Lazaris A.S., Eastman J.A. et al. Alzheimer’s Disease Neuroimaging Initiative. Plasma BDNF levels associate with Pittsburgh compound B binding in the brain. Alzheimers Dement. 2015; 1: 187–93. DOI: 10.1016/j.dadm.2015.01.005
  25. Johnson D., Lanahan A., Buck C.R. et al. Expression and structure of the human NGF receptor. Cell. 1986; 47 (4): 545–54. DOI: 10.1016/0092-8674(86)90619-7
  26. Kaminari A., Giannakas N., Tzinia A. et al. Overexpression of matrix metalloproteinase-9 (MMP-9) rescues insulin-mediated impairment in the 5XFAD model of Alzheimer’s disease. Sci Rep. 2017; 7 (1): 683. DOI: 10.1038/s41598-017-00794-5
  27. Kaplan D.R., Hempstead B.L., Martin-Zanca D. et al. The trk proto-oncogene product: a signal transducing receptor for nerve growth factor. Science. 1991; 252 (5005): 554–8. DOI: 10.1126/science.1850549
  28. Kim H.S., Jeon I., Noh J.E. et al. Intracerebral Transplantation of BDNF-overexpressing Human Neural Stem Cells (HB1.F3.BDNF) Promotes Migration, Differentiation and Functional Recovery in a Rodent Model of Huntington’s Disease. Exp Neurobiol. 2020; 29 (2): 130–7. DOI: 10.5607/en20011
  29. Kopec B.M., Zhao L., Rosa-Molinar E. et al. Non-invasive Brain Delivery and Efficacy of BDNF in APP/PS1 Transgenic Mice as a Model of Alzheimer’s Disease. Med Res Arch. 2020; 8 (2): 2043. DOI: 10.18103/mra.v8i2.2043
  30. Lesniak A., Poznański P., Religa P. et al. Loss of Brain-Derived Neurotrophic Factor (BDNF) Resulting From Congenital- Or Mild Traumatic Brain Injury-Induced Blood-Brain Barrier Disruption Correlates With Depressive-Like Behaviour. Neuroscience. 2021; 17: S0306-4522(21)00020-8. DOI: 10.1016/j.neuroscience.2021.01.013
  31. Lu B., Nagappan G., Lu Y. BDNF and synaptic plasticity, cognitive function, and dysfunction. Handb Exp Pharmacol. 2014; 220: 223–50. DOI: 10.1007/978-3-642-45106-5_9
  32. Naegelin Y., Saeuberli K., Schaedelin S. et al. Levels of brain-derived neurotrophic factor in patients with multiple sclerosis. Ann Clin Transl Neurol. 2020; 7 (11): 2251–61. DOI: 10.1002/acn3.51215
  33. Nguyen K.Q., Rymar V.V., Sadikot A.F. Impaired TrkB Signaling Underlies Reduced BDNF-Mediated Trophic Support of Striatal Neurons in the R6/2 Mouse Model of Huntington’s Disease. Front Cell Neurosci. 2016; 10: 37. DOI: 10.3389/fncel.2016.00037
  34. Miranda M., Morici J.F., Zanoni M.B. et al. Brain-derived neurotrophic factor: a key molecule for memory in the healthy and the pathological brain. Front Cell Neurosci. 2019; 13: 363. DOI: 10.3389/fncel.2019.00363
  35. Paillard T., Rolland Y., de Souto Barreto P. Protective Effects of Physical Exercise in Alzheimer’s Disease and Parkinson’s Disease: A Narrative Review. J Clin Neurol. 2015; 11 (3): 212–9. DOI: 10.3988/jcn.2015.11.3.212
  36. Palasz E., Wysocka A., Gasiorowska A. et al. BDNF as a Promising Therapeutic Agent in Parkinson’s Disease. Int J Mol Sci. 2020; 21 (3): 1170. DOI: 10.3390/ijms21031170
  37. Palma-Álvarez R.F., Ros-Cucurull E., Amaro-Hosey K. et al. Peripheral levels of BDNF and opiate-use disorder: literature review and update. Rev Neurosci. 2017; 28 (5): 499–508.
  38. Pins B., Cifuentes-Diaz C., Farah A.T. et al. Conditional BDNF Delivery from Astrocytes Rescues Memory Deficits, Spine Density, and Synaptic Properties in the 5xFAD Mouse Model of Alzheimer Disease. J Neurosci. 2019; 39 (13): 2441–58. DOI: 10.1523/JNEUROSCI.2121-18.2019
  39. Rios M. Neurotrophins and the regulation of energy balance and body weight. Handb Exp Pharmacol. 2014; 220: 283–307. DOI: 10.1007/978-3-642-45106-5_11
  40. Satomura E., Baba H., Nakano Y. et al. Correlations between brain-derived neurotrophic factor and clinical symptoms in medicated patients with major depression. J Affect Disord. 2011; 135 (1-3): 332–5. DOI: 10.1016/j.jad.2011.06.041
  41. Sheeler C., Rosa J.G., Borgenheimer E. et al. Post-symptomatic Delivery of Brain-Derived Neurotrophic Factor (BDNF) Ameliorates Spinocerebellar Ataxia Type 1 (SCA1) Pathogenesis. Cerebellum. 2021; Online ahead of print. DOI: 10.1007/s12311-020-01226-3
  42. Song J.H, Yu J.T., Tan L. Brain-derived neurotrophic factor in Alzheimer’s disease: risk, mechanisms, and therapy. Mol Neurobiol. 2015; 52: 1477–93. DOI: 10.1007/s12035-014-8958-4
  43. Sordyl J., Kopyta I., Sarecka-Hujar B. et al. Lipid levels and selected biomarkers of vascular changes in children with idiopathic headaches – a preliminary report. Arch Med Sci. 2019; 15 (1): 120–5. DOI: 10.5114/aoms.2018.73983
  44. Tanure M.T., Gomez R.S., Hurtado R.C. et al. Increased serum levels of brain-derived neurotropic factor during migraine attacks: a pilot study. J Headache Pain. 2010; 11 (5): 427–30. DOI: 10.1007/s10194-010-0233-0
  45. Toda T., Gage F.H. Review: adult neurogenesis contributes to hippocampal plasticity. Cell Tissue Res. 2017; 373: 693–709. DOI: 10.1007/s00441-017-2735-4
  46. Ventriglia M., Zanardini R., Bonomini C. et al. Serum brain-derived neurotrophic factor levels in different neurological diseases. Biomed Res Int. 2013; 2013: 901082. DOI: 10.1155/2013/901082
  47. Weinstein G., Preis S.R., Beiser A.S. et al. Clinical and environmental correlates of serum BDNF: a descriptive study with plausible implications for AD research. Curr Alzheimer Res. 2017; 14: 722–30. DOI: 10.2174/1567205014666170203094520
  48. Zaman Emon M.P., Das R., Nishuty N.L..et al. Reduced serum BDNF levels are associated with the increased risk for developing MDD: a case-control study with or without antidepressant therapy. Res Notes. 2021; 13 (1): 83. DOI: 10.1186/s13104-020-04952-3
  49. Zhang X., Xue Y., Li J. et al. The involvement of ADAR1 in antidepressant action by regulating BDNF via miR-432. Behav Brain Res. 2021; 402: 113087. DOI: 10.1016/j.bbr.2020.113087
  50. Zhang Z., Liu X., Schroeder J.P. et al. 7,8-Dihydroxyflavone prevents synaptic loss and memory deficits in a mouse model of Alzheimer’s disease. Neuropsychopharmacology. 2014; 39 (3): 638–50. DOI: 10.1038/npp.2013.243