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Gene Review

Bdnf  -  brain derived neurotrophic factor

Mus musculus

Synonyms: BDNF, Brain-derived neurotrophic factor


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Disease relevance of Bdnf


Psychiatry related information on Bdnf


High impact information on Bdnf

  • Mouse Bdnf gene includes six bipartite transcripts that are generated by six independently transcribed exons, each of which is spliced to a major coding exon and a tripartite transcript that is composed of two upstream exons and one coding exon [10]. No evidence of primate BDNFOS gene lncRNA was found in mouse and rat genome and transcripts  [10].
  • Our findings indicate that a key role of huntingtin is to promote BDNF transport and suggest that loss of this function might contribute to pathogenesis [11].
  • BDNF regulates the maturation of inhibition and the critical period of plasticity in mouse visual cortex [7].
  • In contrast with mice lacking the BDNF receptor TrkB, motor neurons appear normal in the BDNF mutant [12].
  • Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development [12].
  • This mutation eliminates expression of gp145trkB, a protein-tyrosine kinase that serves as the signaling receptor for two members of the nerve growth factor family of neurotrophins, brain-derived neurotrophic factor and neurotrophin-4 [13].
  • Physical exercise, not non-physical environmental enrichment,  is the critical factor mediating increased BDNF protein levels in adult mouse hippocampal neurogenesis  [14].

Chemical compound and disease context of Bdnf


Biological context of Bdnf


Anatomical context of Bdnf

  • Interneurons were also abundant in differentiating OB neural stem cell cultures; the neurons responded to the neurotrophin Bdnf and expressed presynaptic proteins [25].
  • These data suggest that expression of Bdnf is dependent on ATOH1 protein in some but does not require ATOH1 protein in other inner ear cells [26].
  • E18.5 Atoh1 null mice have many afferent fibers to the apex of the cochlea, the anterior and the posterior crista, all areas with numerous Bdnf-beta-galactosidase-positive cells [26].
  • Few fibers remain to the saccule, utricle, and the base of the cochlea, all areas with few or no Bdnf-beta-galactosidase-positive cells [26].
  • ErbB2 null mice retain afferents to inner hair cells possibly because of the prominent expression of the neurotrophin Bdnf in developing hair cells [27].

Associations of Bdnf with chemical compounds


Physical interactions of Bdnf


Enzymatic interactions of Bdnf


Co-localisations of Bdnf


Regulatory relationships of Bdnf

  • Our results show that NT3 expressed emporally and spatially in the place of BDNF is sufficient in some neuronal populations to compensate for the loss of BDNF [36].
  • 4. Absence of BDNF induced a reduction of NR2A level [37].
  • K252a, a protein kinase inhibitor, reduced the NT-4- and BDNF-induced response of the NIH3T3/trkB cells [38].
  • Here, we report that BDNF stimulates the expression of tissue-type plasminogen activator (tPA) in primary cultures of cortical neurons in a time- and concentration-dependent manner [39].
  • Although the BDNF-induced GABAA receptor internalization was sensitive to K252a, it did not become manifest until 5 min after exposure to BDNF [30].

Other interactions of Bdnf

  • In these assays, BDNF elicits a response at least two orders of magnitude higher than NT-3 [20].
  • Furthermore, the BDNF dose dependency displayed by these TrkB-expressing fibroblasts is similar to that required to support the survival of primary neurons [40].
  • Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4 [21].
  • Early failure of cerebellar BDNF expression may be related to the ataxic phenotype in stg mice [22].
  • Our data confirm an unexpectedly high proportion of sensory neuron losses in NT-3 (>70%), BDNF (>20%), and TrkC (>30%) mutants, which encompass populations thought to be NGF-dependent [41].

Analytical, diagnostic and therapeutic context of Bdnf


  1. Stroke damage in mice after knocking the neutrophin-4 gene into the brain-derived neurotrophic factor locus. Endres, M., Fan, G., Hirt, L., Jaenisch, R. J. Cereb. Blood Flow Metab. (2003) [Pubmed]
  2. Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 complement and cooperate with each other sequentially during visceral neuron development. ElShamy, W.M., Ernfors, P. J. Neurosci. (1997) [Pubmed]
  3. Differential effects of voluntary physical exercise on behavioral and brain-derived neurotrophic factor expression deficits in Huntington's disease transgenic mice. Pang, T.Y., Stam, N.C., Nithianantharajah, J., Howard, M.L., Hannan, A.J. Neuroscience (2006) [Pubmed]
  4. Site-specific interactions of neurotrophin-3 and fibroblast growth factor (FGF2) in the embryonic development of the mouse cochlear nucleus. Hossain, W.A., D'Sa, C., Morest, D.K. J. Neurobiol. (2006) [Pubmed]
  5. Brain-derived neurotrophic factor facilitates in vivo internalization of tetanus neurotoxin C-terminal fragment fusion proteins in mature mouse motor nerve terminals. Roux, S., Saint Cloment, C., Curie, T., Girard, E., Mena, F.J., Barbier, J., Osta, R., Molg??, J., Br??let, P. Eur. J. Neurosci. (2006) [Pubmed]
  6. BDNF heterozygous mice demonstrate age-related changes in striatal and nigral gene expression. Saylor, A.J., Meredith, G.E., Vercillo, M.S., Zahm, D.S., McGinty, J.F. Exp. Neurol. (2006) [Pubmed]
  7. BDNF regulates the maturation of inhibition and the critical period of plasticity in mouse visual cortex. Huang, Z.J., Kirkwood, A., Pizzorusso, T., Porciatti, V., Morales, B., Bear, M.F., Maffei, L., Tonegawa, S. Cell (1999) [Pubmed]
  8. Brain-derived neurotrophic factor regulates glucose metabolism by modulating energy balance in diabetic mice. Nakagawa, T., Tsuchida, A., Itakura, Y., Nonomura, T., Ono, M., Hirota, F., Inoue, T., Nakayama, C., Taiji, M., Noguchi, H. Diabetes (2000) [Pubmed]
  9. BDNF regulates the expression of fragile X mental retardation protein mRNA in the hippocampus. Castrén, M., Lampinen, K.E., Miettinen, R., Koponen, E., Sipola, I., Bakker, C.E., Oostra, B.A., Castrén, E. Neurobiol. Dis. (2002) [Pubmed]
  10. Rodent BDNF genes, novel promoters, novel splice variants, and regulation by cocaine. Liu, Q.R., Lu, L., Zhu, X.G., Gong, J.P., Shaham, Y., Uhl, G.R. Brain. Res. (2006) [Pubmed]
  11. Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Gauthier, L.R., Charrin, B.C., Borrell-Pagès, M., Dompierre, J.P., Rangone, H., Cordelières, F.P., De Mey, J., MacDonald, M.E., Lessmann, V., Humbert, S., Saudou, F. Cell (2004) [Pubmed]
  12. Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development. Jones, K.R., Fariñas, I., Backus, C., Reichardt, L.F. Cell (1994) [Pubmed]
  13. Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal death. Klein, R., Smeyne, R.J., Wurst, W., Long, L.K., Auerbach, B.A., Joyner, A.L., Barbacid, M. Cell (1993) [Pubmed]
  14. Running is the neurogenic and neurotrophic stimulus in environmental enrichment. Kobilo, T., Liu, Q.R., Gandhi, K., Mughal, M., Shaham, Y., van Praag, H. Learn. Mem. (2011) [Pubmed]
  15. The immunomodulator glatiramer acetate augments the expression of neurotrophic factors in brains of experimental autoimmune encephalomyelitis mice. Aharoni, R., Eilam, R., Domev, H., Labunskay, G., Sela, M., Arnon, R. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  16. Brain-derived neurotrophic factor improves blood glucose control and alleviates fasting hyperglycemia in C57BLKS-Lepr(db)/lepr(db) mice. Tonra, J.R., Ono, M., Liu, X., Garcia, K., Jackson, C., Yancopoulos, G.D., Wiegand, S.J., Wong, V. Diabetes (1999) [Pubmed]
  17. Direct evidence for the involvement of brain-derived neurotrophic factor in the development of a neuropathic pain-like state in mice. Yajima, Y., Narita, M., Usui, A., Kaneko, C., Miyatake, M., Narita, M., Yamaguchi, T., Tamaki, H., Wachi, H., Seyama, Y., Suzuki, T. J. Neurochem. (2005) [Pubmed]
  18. Neuroprotection of immortalized hippocampal neurones by brain-derived neurotrophic factor and Raf-1 protein kinase: role of extracellular signal-regulated protein kinase and phosphatidylinositol 3-kinase. Rössler, O.G., Giehl, K.M., Thiel, G. J. Neurochem. (2004) [Pubmed]
  19. Correlated long-term increase of brain-derived neurotrophic factor and Trk B proteins in enlarged granule cells of mouse hippocampus after kainic acid injection. Inoue, T., Hirai, H., Onteniente, B., Suzuki, F. Neuroscience (1998) [Pubmed]
  20. The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3. Klein, R., Nanduri, V., Jing, S.A., Lamballe, F., Tapley, P., Bryant, S., Cordon-Cardo, C., Jones, K.R., Reichardt, L.F., Barbacid, M. Cell (1991) [Pubmed]
  21. Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4. Conover, J.C., Erickson, J.T., Katz, D.M., Bianchi, L.M., Poueymirou, W.T., McClain, J., Pan, L., Helgren, M., Ip, N.Y., Boland, P. Nature (1995) [Pubmed]
  22. Selective failure of brain-derived neurotrophic factor mRNA expression in the cerebellum of stargazer, a mutant mouse with ataxia. Qiao, X., Hefti, F., Knusel, B., Noebels, J.L. J. Neurosci. (1996) [Pubmed]
  23. Cerebellar brain-derived neurotrophic factor-TrkB defect associated with impairment of eyeblink conditioning in Stargazer mutant mice. Qiao, X., Chen, L., Gao, H., Bao, S., Hefti, F., Thompson, R.F., Knusel, B. J. Neurosci. (1998) [Pubmed]
  24. A new role for neurotrophins: involvement of brain-derived neurotrophic factor and neurotrophin-4 in hair cycle control. Botchkarev, V.A., Botchkareva, N.V., Welker, P., Metz, M., Lewin, G.R., Subramaniam, A., Bulfone-Paus, S., Hagen, E., Braun, A., Lommatzsch, M., Renz, H., Paus, A.R. FASEB J. (1999) [Pubmed]
  25. Generation of GABAergic and dopaminergic interneurons from endogenous embryonic olfactory bulb precursor cells. Verga??o-Vera, E., Yusta-Boyo, M.J., de Castro, F., Bernad, A., de Pablo, F., Vicario-Abej??n, C. Development (2006) [Pubmed]
  26. Atoh1 null mice show directed afferent fiber growth to undifferentiated ear sensory epithelia followed by incomplete fiber retention. Fritzsch, B., Matei, V.A., Nichols, D.H., Bermingham, N., Jones, K., Beisel, K.W., Wang, V.Y. Dev. Dyn. (2005) [Pubmed]
  27. A disorganized innervation of the inner ear persists in the absence of ErbB2. Morris, J.K., Maklad, A., Hansen, L.A., Feng, F., Sorensen, C., Lee, K.F., Macklin, W.B., Fritzsch, B. Brain Res. (2006) [Pubmed]
  28. BDNF but not NT-4 is required for normal flexion reflex plasticity and function. Heppenstall, P.A., Lewin, G.R. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  29. Brain-derived neurotrophic factor regulates the expression of D1 dopamine receptors. Do, T., Kerr, B., Kuzhikandathil, E.V. J. Neurochem. (2007) [Pubmed]
  30. Brain-derived neurotrophic factor attenuates mouse cerebellar granule cell GABA(A) receptor-mediated responses via postsynaptic mechanisms. Cheng, Q., Yeh, H.H. J. Physiol. (Lond.) (2003) [Pubmed]
  31. Brain-derived neurotrophic factor is present in adult mouse taste cells with synapses. Yee, C.L., Jones, K.R., Finger, T.E. J. Comp. Neurol. (2003) [Pubmed]
  32. c-jun is essential for sympathetic neuronal death induced by NGF withdrawal but not by p75 activation. Palmada, M., Kanwal, S., Rutkoski, N.J., Gustafson-Brown, C., Johnson, R.S., Wisdom, R., Carter, B.D., Gufstafson-Brown, C. J. Cell Biol. (2002) [Pubmed]
  33. TrkB mutant lacking the amino-terminal half of the extracellular portion acts as a functional brain-derived neurotrophic factor receptor. Kojima, S., Nakayama, T., Kuwajima, G., Suzuki, H., Sakata, T. Biochim. Biophys. Acta (1999) [Pubmed]
  34. Brain-derived neurotrophic factor stimulates phosphorylation of stathmin in cortical neurons. Cardinaux, J.R., Magistretti, P.J., Martin, J.L. Brain Res. Mol. Brain Res. (1997) [Pubmed]
  35. Evidence that brain-derived neurotrophic factor from presynaptic nerve terminals regulates the phenotype of calbindin-containing neurons in the lateral septum. Fawcett, J.P., Alonso-Vanegas, M.A., Morris, S.J., Miller, F.D., Sadikot, A.F., Murphy, R.A. J. Neurosci. (2000) [Pubmed]
  36. Differential influence of BDNF and NT3 on the expression of calcium binding proteins and neuropeptide Y in vivo. Agerman, K., Ernfors, P. Neuroreport (2003) [Pubmed]
  37. NR2A but not NR2B N-methyl-D-aspartate receptor subunit is altered in the visual cortex of BDNF-knock-out mice. Margottil, E., Domenici, L. Cell. Mol. Neurobiol. (2003) [Pubmed]
  38. Interaction of NT-4 and BDNF with gp145trkb receptor: effect on cellular metabolism. Hopkins, M.A., Rosser, M.P., Fernandes, P.B., Bursuker, I. J. Neurosci. Methods (1997) [Pubmed]
  39. BDNF stimulates expression, activity and release of tissue-type plasminogen activator in mouse cortical neurons. Fiumelli, H., Jabaudon, D., Magistretti, P.J., Martin, J.L. Eur. J. Neurosci. (1999) [Pubmed]
  40. TrkB mediates BDNF/NT-3-dependent survival and proliferation in fibroblasts lacking the low affinity NGF receptor. Glass, D.J., Nye, S.H., Hantzopoulos, P., Macchi, M.J., Squinto, S.P., Goldfarb, M., Yancopoulos, G.D. Cell (1991) [Pubmed]
  41. Absence of sensory neurons before target innervation in brain-derived neurotrophic factor-, neurotrophin 3-, and TrkC-deficient embryonic mice. Liebl, D.J., Tessarollo, L., Palko, M.E., Parada, L.F. J. Neurosci. (1997) [Pubmed]
  42. Novel roles for neurotrophins are suggested by BDNF and NT-3 mRNA expression in developing neurons. Schecterson, L.C., Bothwell, M. Neuron (1992) [Pubmed]
  43. Brain-derived neurotrophic factor levels in the nervous system of wild-type and neurotrophin gene mutant mice. Kolbeck, R., Bartke, I., Eberle, W., Barde, Y.A. J. Neurochem. (1999) [Pubmed]
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