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Bdnf  -  brain-derived neurotrophic factor

Rattus norvegicus

Synonyms: BDNF, Brain-derived neurotrophic factor
 
 
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Disease relevance of Bdnf

  • BDNF seems to be a trophic factor for mesencephalic dopaminergic neurons, increasing their survival, including that of neuronal cells which degenerate in Parkinson's disease [1].
  • PNT-1 also promoted survival of a greater number of embryonic dorsal root ganglion neurons than any of the other neurotrophins alone, and its effects were equivalent to a combination of NGF, BDNF, and NT-3 [2].
  • BDNF and NT-3 decreased body weights, an effect that was sustained over the infusion period [3].
  • Brain-derived neurotrophic factor activation of TrkB protects neuroblastoma cells from chemotherapy-induced apoptosis via phosphatidylinositol 3'-kinase pathway [4].
  • Ischemia and reperfusion increased hippocampal levels of BDNF [5].
 

Psychiatry related information on Bdnf

 

High impact information on Bdnf

  • Thus trkB encodes an essential component of a functional receptor for BDNF and NT-3, but not for NGF [10].
  • BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization [11].
  • A more diverse role for BDNF has emerged progressively from observations showing that it is also transported anterogradely, is released on neuron depolarization, and triggers rapid intracellular signals and action potentials in central neurons [11].
  • Using lesions and gene-targeted mice lacking BDNF, we show that BDNF from dopamine neurons is responsible for inducing normal expression of the dopamine D3 receptor in nucleus accumbens both during development and in adulthood [11].
  • We found that BDNF and neurotrophin-4/5 depolarized neurons just as rapidly as the neurotransmitter glutamate, even at a more than thousand-fold lower concentration [12].
 

Chemical compound and disease context of Bdnf

 

Biological context of Bdnf

 

Anatomical context of Bdnf

 

Associations of Bdnf with chemical compounds

  • Although proneurotrophins have been considered inactive precursors, we show here that the proforms of nerve growth factor (NGF) and the proforms of brain derived neurotrophic factor (BDNF) are secreted and cleaved extracellularly by the serine protease plasmin and by selective matrix metalloproteinases (MMPs) [22].
  • In contrast to BDNF, the action of NT4 was independent of calcium influx through NMDA receptors and L-type calcium channels [20].
  • Brain-derived neurotrophic factor regulates expression of androgen receptors in perineal motoneurons [23].
  • The effects of BDNF and NT-3 on dopamine uptake activity showed no additivity [24].
  • In PCA-lesioned rats, intracortical infusions of BDNF completely prevented the severe neurotoxin-induced loss of 5-HT axons near the infusion cannula [25].
 

Physical interactions of Bdnf

 

Enzymatic interactions of Bdnf

  • In contrast, multiple bolus microinjections of BDNF accelerated kindling development and did not affect the level of phosphorylated Trks or TrkB receptors [29].
  • In contrast to shams, the acutely exercised FPI rats failed to show activity-dependent BDNF upregulation and had significant decreases of phosphorylated synapsin I and total CREB [30].
  • These factors may act as the eventual repressors for BDNF expression via competition and heterodimerization with phosphorylated CREB, a transcription factor important for BDNF expression [31].
  • Shp-2 specifically regulates several tyrosine-phosphorylated proteins in brain-derived neurotrophic factor signaling in cultured cerebral cortical neurons [27].
 

Co-localisations of Bdnf

 

Regulatory relationships of Bdnf

  • The data presented are the first demonstration that one neurotrophin regulates the expression of another and provide evidence that NT-3 production in granule neurons is regulated by both BDNF and T3 [35].
  • Intracerebroventricular BDNF injections (5 microg/rat) in non-anesthetized adult male rats induce a gradual increase in the CRH mRNA signal whereas AVP mRNA signal progressively decreases in the parvocellular and magnocellular PVN portions [32].
  • Long-term potentiation in the dentate gyrus of the rat hippocampus is accompanied by brain-derived neurotrophic factor-induced activation of TrkB [36].
  • AMPA protects cultured neurons against glutamate excitotoxicity through a phosphatidylinositol 3-kinase-dependent activation in extracellular signal-regulated kinase to upregulate BDNF gene expression [37].
  • The distribution of BDNF-induced neuropeptide Y immunoreactivity is similar to the pattern observed in animals submitted to hippocampal kindling, with the exception of mossy fibres which only become immunoreactive following seizure activity [38].
 

Other interactions of Bdnf

  • We find that NT-3 injected locally specifically enhances this sprouting, whereas BDNF has no effect [21].
  • A marked increase of BDNF and NT-4 mRNAs in the distal segment of the sciatic nerve was seen 2 wk after the lesion [39].
  • Transcellular induction of neuropeptide Y expression by NT4 and BDNF [20].
  • BDNF protein was rapidly upregulated within 24 hr after lesion, whereas CNTF protein upregulation was delayed reaching maximal levels by 3 d [40].
  • Because sustained [Ca2+]i is believed to be causally related to neuronal injury, we suggest that BDNF and FGF2 may protect cerebellar granule cells against excitotoxicity by altering the NMDA receptor-Ca2+ signaling via a downregulation of NMDA receptor subunit expression [41].
 

Analytical, diagnostic and therapeutic context of Bdnf

References

  1. BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Hyman, C., Hofer, M., Barde, Y.A., Juhasz, M., Yancopoulos, G.D., Squinto, S.P., Lindsay, R.M. Nature (1991) [Pubmed]
  2. Pan-neurotrophin 1: a genetically engineered neurotrophic factor displaying multiple specificities in peripheral neurons in vitro and in vivo. Ilag, L.L., Curtis, R., Glass, D., Funakoshi, H., Tobkes, N.J., Ryan, T.E., Acheson, A., Lindsay, R.M., Persson, H., Yancopoulos, G.D. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  3. Brain-derived neurotrophic factor and neurotrophin-3 activate striatal dopamine and serotonin metabolism and related behaviors: interactions with amphetamine. Martin-Iverson, M.T., Todd, K.G., Altar, C.A. J. Neurosci. (1994) [Pubmed]
  4. Brain-derived neurotrophic factor activation of TrkB protects neuroblastoma cells from chemotherapy-induced apoptosis via phosphatidylinositol 3'-kinase pathway. Jaboin, J., Kim, C.J., Kaplan, D.R., Thiele, C.J. Cancer Res. (2002) [Pubmed]
  5. Hypothermic reperfusion after cardiac arrest augments brain-derived neurotrophic factor activation. D'Cruz, B.J., Fertig, K.C., Filiano, A.J., Hicks, S.D., DeFranco, D.B., Callaway, C.W. J. Cereb. Blood Flow Metab. (2002) [Pubmed]
  6. Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 prevent the death of striatal projection neurons in a rodent model of Huntington's disease. Pérez-Navarro, E., Canudas, A.M., Akerund, P., Alberch, J., Arenas, E. J. Neurochem. (2000) [Pubmed]
  7. BDNF rescues myosin heavy chain IIB muscle fibers after neonatal nerve injury. Mousavi, K., Parry, D.J., Jasmin, B.J. Am. J. Physiol., Cell Physiol. (2004) [Pubmed]
  8. Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. Wu, A., Ying, Z., Gomez-Pinilla, F. J. Neurotrauma (2004) [Pubmed]
  9. Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. Shirayama, Y., Chen, A.C., Nakagawa, S., Russell, D.S., Duman, R.S. J. Neurosci. (2002) [Pubmed]
  10. trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor. Squinto, S.P., Stitt, T.N., Aldrich, T.H., Davis, S., Bianco, S.M., Radziejewski, C., Glass, D.J., Masiakowski, P., Furth, M.E., Valenzuela, D.M. Cell (1991) [Pubmed]
  11. BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization. Guillin, O., Diaz, J., Carroll, P., Griffon, N., Schwartz, J.C., Sokoloff, P. Nature (2001) [Pubmed]
  12. Neurotrophin-evoked rapid excitation through TrkB receptors. Kafitz, K.W., Rose, C.R., Thoenen, H., Konnerth, A. Nature (1999) [Pubmed]
  13. Spinal brain-derived neurotrophic factor (BDNF) produces hyperalgesia in normal mice while antisense directed against either BDNF or trkB, prevent inflammation-induced hyperalgesia. Groth, R., Aanonsen, L. Pain (2002) [Pubmed]
  14. Efficacy of brain-derived neurotrophic factor and neurotrophin-3 on neurochemical and behavioral deficits associated with partial nigrostriatal dopamine lesions. Altar, C.A., Boylan, C.B., Fritsche, M., Jones, B.E., Jackson, C., Wiegand, S.J., Lindsay, R.M., Hyman, C. J. Neurochem. (1994) [Pubmed]
  15. Involvement of the brain-derived neurotrophic factor/TrkB pathway in neuroprotecive effect of cyclosporin A in forebrain ischemia. Miyata, K., Omori, N., Uchino, H., Yamaguchi, T., Isshiki, A., Shibasaki, F. Neuroscience (2001) [Pubmed]
  16. Nerve growth factor and brain-derived neurotrophic factor mRNAs are regulated in distinct cell populations of rat heart after ischaemia and reperfusion. Hiltunen, J.O., Laurikainen, A., Väkevä, A., Meri, S., Saarma, M. J. Pathol. (2001) [Pubmed]
  17. Neurotrophins promote the survival and development of neurons in the cerebellum of hypothyroid rats in vivo. Neveu, I., Arenas, E. J. Cell Biol. (1996) [Pubmed]
  18. Brain-derived neurotrophic factor restores long-term potentiation in polysialic acid-neural cell adhesion molecule-deficient hippocampus. Muller, D., Djebbara-Hannas, Z., Jourdain, P., Vutskits, L., Durbec, P., Rougon, G., Kiss, J.Z. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  19. Brain-derived neurotrophic factor rapidly enhances synaptic transmission in hippocampal neurons via postsynaptic tyrosine kinase receptors. Levine, E.S., Dreyfus, C.F., Black, I.B., Plummer, M.R. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  20. Transcellular induction of neuropeptide Y expression by NT4 and BDNF. Wirth, M.J., Patz, S., Wahle, P. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  21. Neurotrophin-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesion. Schnell, L., Schneider, R., Kolbeck, R., Barde, Y.A., Schwab, M.E. Nature (1994) [Pubmed]
  22. Regulation of cell survival by secreted proneurotrophins. Lee, R., Kermani, P., Teng, K.K., Hempstead, B.L. Science (2001) [Pubmed]
  23. Brain-derived neurotrophic factor regulates expression of androgen receptors in perineal motoneurons. Al-Shamma, H.A., Arnold, A.P. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  24. Overlapping and distinct actions of the neurotrophins BDNF, NT-3, and NT-4/5 on cultured dopaminergic and GABAergic neurons of the ventral mesencephalon. Hyman, C., Juhasz, M., Jackson, C., Wright, P., Ip, N.Y., Lindsay, R.M. J. Neurosci. (1994) [Pubmed]
  25. Brain-derived neurotrophic factor promotes the survival and sprouting of serotonergic axons in rat brain. Mamounas, L.A., Blue, M.E., Siuciak, J.A., Altar, C.A. J. Neurosci. (1995) [Pubmed]
  26. A calcium/calmodulin kinase pathway connects brain-derived neurotrophic factor to the cyclic AMP-responsive transcription factor in the rat hippocampus. Blanquet, P.R., Mariani, J., Derer, P. Neuroscience (2003) [Pubmed]
  27. Shp-2 specifically regulates several tyrosine-phosphorylated proteins in brain-derived neurotrophic factor signaling in cultured cerebral cortical neurons. Araki, T., Yamada, M., Ohnishi, H., Sano, S., Uetsuki, T., Hatanaka, H. J. Neurochem. (2000) [Pubmed]
  28. The anti-p75 antibody, MC192, and brain-derived neurotrophic factor inhibit nerve growth factor-dependent neurite growth from adult sensory neurons. Kimpinski, K., Jelinski, S., Mearow, K. Neuroscience (1999) [Pubmed]
  29. The effects of brain-derived neurotrophic factor (BDNF) administration on kindling induction, Trk expression and seizure-related morphological changes. Xu, B., Michalski, B., Racine, R.J., Fahnestock, M. Neuroscience (2004) [Pubmed]
  30. Voluntary exercise following traumatic brain injury: brain-derived neurotrophic factor upregulation and recovery of function. Griesbach, G.S., Hovda, D.A., Molteni, R., Wu, A., Gomez-Pinilla, F. Neuroscience (2004) [Pubmed]
  31. Expression profiling to understand actions of NMDA/glutamate receptor antagonists in rat brain. Törönen, P., Storvik, M., Lindén, A.M., Kontkane, O., Marvanová, M., Lakso, M., Castrén, E., Wong, G. Neurochem. Res. (2002) [Pubmed]
  32. A single brain-derived neurotrophic factor injection modifies hypothalamo-pituitary-adrenocortical axis activity in adult male rats. Givalois, L., Naert, G., Rage, F., Ixart, G., Arancibia, S., Tapia-Arancibia, L. Mol. Cell. Neurosci. (2004) [Pubmed]
  33. Synaptic and extrasynaptic localization of brain-derived neurotrophic factor and the tyrosine kinase B receptor in cultured hippocampal neurons. Swanwick, C.C., Harrison, M.B., Kapur, J. J. Comp. Neurol. (2004) [Pubmed]
  34. Sorting of vesicular monoamine transporter 2 to the regulated secretory pathway confers the somatodendritic exocytosis of monoamines. Li, H., Waites, C.L., Staal, R.G., Dobryy, Y., Park, J., Sulzer, D.L., Edwards, R.H. Neuron (2005) [Pubmed]
  35. Brain-derived neurotrophic factor increases neurotrophin-3 expression in cerebellar granule neurons. Leingärtner, A., Heisenberg, C.P., Kolbeck, R., Thoenen, H., Lindholm, D. J. Biol. Chem. (1994) [Pubmed]
  36. Long-term potentiation in the dentate gyrus of the rat hippocampus is accompanied by brain-derived neurotrophic factor-induced activation of TrkB. Gooney, M., Lynch, M.A. J. Neurochem. (2001) [Pubmed]
  37. AMPA protects cultured neurons against glutamate excitotoxicity through a phosphatidylinositol 3-kinase-dependent activation in extracellular signal-regulated kinase to upregulate BDNF gene expression. Wu, X., Zhu, D., Jiang, X., Okagaki, P., Mearow, K., Zhu, G., McCall, S., Banaudha, K., Lipsky, R.H., Marini, A.M. J. Neurochem. (2004) [Pubmed]
  38. Overexpression of neuropeptide Y induced by brain-derived neurotrophic factor in the rat hippocampus is long lasting. Reibel, S., Vivien-Roels, B., Lê, B.T., Larmet, Y., Carnahan, J., Marescaux, C., Depaulis, A. Eur. J. Neurosci. (2000) [Pubmed]
  39. Differential expression of mRNAs for neurotrophins and their receptors after axotomy of the sciatic nerve. Funakoshi, H., Frisén, J., Barbany, G., Timmusk, T., Zachrisson, O., Verge, V.M., Persson, H. J. Cell Biol. (1993) [Pubmed]
  40. Changes in neurotrophic factor expression and receptor activation following exposure of hippocampal neuron/astrocyte cocultures to kainic acid. Rudge, J.S., Pasnikowski, E.M., Holst, P., Lindsay, R.M. J. Neurosci. (1995) [Pubmed]
  41. Brain-derived neurotrophic factor and basic fibroblast growth factor downregulate NMDA receptor function in cerebellar granule cells. Brandoli, C., Sanna, A., De Bernardi, M.A., Follesa, P., Brooker, G., Mocchetti, I. J. Neurosci. (1998) [Pubmed]
  42. Brain-derived neurotrophic factor and neurotrophin 3 mRNAs in the peripheral target fields of developing inner ear ganglia. Pirvola, U., Ylikoski, J., Palgi, J., Lehtonen, E., Arumäe, U., Saarma, M. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  43. The survival-promoting effect of glial cell line-derived neurotrophic factor on axotomized corticospinal neurons in vivo is mediated by an endogenous brain-derived neurotrophic factor mechanism. Giehl, K.M., Schütte, A., Mestres, P., Yan, Q. J. Neurosci. (1998) [Pubmed]
  44. Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. Smith, M.A., Makino, S., Kvetnansky, R., Post, R.M. J. Neurosci. (1995) [Pubmed]
 
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