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Gene Review

Ntf4  -  neurotrophin 4

Rattus norvegicus

Synonyms: NT-4, NT-5, NT4P, Neurotrophin-4, Neurotrophin-5, ...
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Disease relevance of Ntf5


Psychiatry related information on Ntf5


High impact information on Ntf5

  • 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 [8].
  • Muscle-derived neurotrophin-4 as an activity-dependent trophic signal for adult motor neurons [9].
  • The production of neurotrophin-4 (NT-4) in rat skeletal muscle was found to depend on muscle activity [9].
  • NT-4 immunoreactivity was detected in slow, type I muscle fibers [9].
  • The expression of NT-3 and NT-4 and their receptors in the trigeminal system prior to target field innervation suggests that these NTFs have also other functions than being the target-derived trophic factors [10].

Chemical compound and disease context of Ntf5


Biological context of Ntf5


Anatomical context of Ntf5

  • Levels of NT-4 mRNA in the whisker pad decrease between embryonic day 13 (E13) and E20, correlating in time with the onset of naturally occurring neuronal death in the innervating trigeminal ganglion [14].
  • The nucleus contained NT3 and cytosol contained NT4 [19].
  • The cytoplasm of conjunctival stratified squamous cells and goblet cell lateral membranes contained NGF, BDNF, and NT4 [19].
  • BDNF and NT-4 differentiate two pathways in the modulation of neuropeptide protein levels in postnatal hippocampal interneurons [20].
  • Among the other factors tested, we also found that NT-4 and GDNF increased the number of surviving neurons in a dose-dependent manner, whereas NGF, BDNF and NT-3 showed no survival promoting effect on corticospinal motor neurons [21].

Associations of Ntf5 with chemical compounds

  • In contrast to BDNF, the action of NT4 was independent of calcium influx through NMDA receptors and L-type calcium channels [16].
  • NT-4/5 treatment elicited the greatest increase (7-fold) in the number of TH-positive neurons, as well as a 2.6-fold increase in dopamine content [22].
  • BDNF, NT-3, or NT-4/5 also produced dose-dependent elevations of 2-3-fold in GABA uptake activity [22].
  • Neurotrophin-4/5 enhances survival of cultured spiral ganglion neurons and protects them from cisplatin neurotoxicity [1].
  • BDNF and NT-4/5 also circumvented glutamate-induced oxidative death in DIV 1-2 granule neurons [23].

Physical interactions of Ntf5

  • A rapid activation of TrkB (1-8 h) was also observed in the spinal cord after axotomy,while the amount of TrkB co-precipitating with NT-4 was markedly lower after axotomy [24].

Regulatory relationships of Ntf5


Other interactions of Ntf5


Analytical, diagnostic and therapeutic context of Ntf5


  1. Neurotrophin-4/5 enhances survival of cultured spiral ganglion neurons and protects them from cisplatin neurotoxicity. Zheng, J.L., Stewart, R.R., Gao, W.Q. J. Neurosci. (1995) [Pubmed]
  2. Expression of trkB mRNA is altered in rat hippocampus after experimental brain trauma. Hicks, R.R., Zhang, L., Dhillon, H.S., Prasad, M.R., Seroogy, K.B. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  3. Neurotrophins: peripherally and centrally acting modulators of tactile stimulus-induced inflammatory pain hypersensitivity. Mannion, R.J., Costigan, M., Decosterd, I., Amaya, F., Ma, Q.P., Holstege, J.C., Ji, R.R., Acheson, A., Lindsay, R.M., Wilkinson, G.A., Woolf, C.J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  4. Neuronal injury increases retrograde axonal transport of the neurotrophins to spinal sensory neurons and motor neurons via multiple receptor mechanisms. Curtis, R., Tonra, J.R., Stark, J.L., Adryan, K.M., Park, J.S., Cliffer, K.D., Lindsay, R.M., DiStefano, P.S. Mol. Cell. Neurosci. (1998) [Pubmed]
  5. Effects of trkB and trkC neurotrophin receptor agonists on thermal nociception: a behavioral and electrophysiological study. Shu, X.Q., Llinas, A., Mendell, L.M. Pain (1999) [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. Differential effects of cortical neurotrophic factors on development of lateral geniculate nucleus and superior colliculus neurons: anterograde and retrograde actions. Wahle, P., Di Cristo, G., Schwerdtfeger, G., Engelhardt, M., Berardi, N., Maffei, L. Development (2003) [Pubmed]
  8. Neurotrophin-evoked rapid excitation through TrkB receptors. Kafitz, K.W., Rose, C.R., Thoenen, H., Konnerth, A. Nature (1999) [Pubmed]
  9. Muscle-derived neurotrophin-4 as an activity-dependent trophic signal for adult motor neurons. Funakoshi, H., Belluardo, N., Arenas, E., Yamamoto, Y., Casabona, A., Persson, H., Ibáñez, C.F. Science (1995) [Pubmed]
  10. Neurotrophins and their receptors in rat peripheral trigeminal system during maxillary nerve growth. Arumäe, U., Pirvola, U., Palgi, J., Kiema, T.R., Palm, K., Moshnyakov, M., Ylikoski, J., Saarma, M. J. Cell Biol. (1993) [Pubmed]
  11. Neurotrophin-4/5 protects hippocampal and cortical neurons against energy deprivation- and excitatory amino acid-induced injury. Cheng, B., Goodman, Y., Begley, J.G., Mattson, M.P. Brain Res. (1994) [Pubmed]
  12. Malonate-induced cortico-motoneuron death is attenuated by NT-4, but not by BDNF or NT-3. Van Westerlaak, M.G., Bär, P.R., Cools, A.R., Joosten, E.A. Neuroreport (2001) [Pubmed]
  13. Protective effects of neurotrophin-4/5 and transforming growth factor-alpha on striatal neuronal phenotypic degeneration after excitotoxic lesioning with quinolinic acid. Alexi, T., Venero, J.L., Hefti, F. Neuroscience (1997) [Pubmed]
  14. Neurotrophin-4 is a target-derived neurotrophic factor for neurons of the trigeminal ganglion. Ibáñez, C.F., Ernfors, P., Timmusk, T., Ip, N.Y., Arenas, E., Yancopoulos, G.D., Persson, H. Development (1993) [Pubmed]
  15. Brain-derived neurotrophic factor and neurotrophin-4/5 modify neurotransmitter-related gene expression in the 6-hydroxydopamine-lesioned rat striatum. Sauer, H., Wong, V., Björklund, A. Neuroscience (1995) [Pubmed]
  16. 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]
  17. The neurotrophins BDNF, NT-3 and NT-4/5, but not NGF, up-regulate the cholinergic phenotype of developing motor neurons. Wong, V., Arriaga, R., Ip, N.Y., Lindsay, R.M. Eur. J. Neurosci. (1993) [Pubmed]
  18. Embryonic geniculate ganglion neurons in culture have neurotrophin-specific electrophysiological properties. Al-Hadlaq, S.M., Bradley, R.M., MacCallum, D.K., Mistretta, C.M. Neuroscience (2003) [Pubmed]
  19. Role of neurotrophins and neurotrophin receptors in rat conjunctival goblet cell secretion and proliferation. Ríos, J.D., Ghinelli, E., Gu, J., Hodges, R.R., Dartt, D.A. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
  20. BDNF and NT-4 differentiate two pathways in the modulation of neuropeptide protein levels in postnatal hippocampal interneurons. Marty, S., Onténiente, B. Eur. J. Neurosci. (1999) [Pubmed]
  21. Neurotrophin-4 (NT-4) and glial cell line-derived neurotrophic factor (GDNF) promote the survival of corticospinal motor neurons of neonatal rats in vitro. Junger, H., Varon, S. Brain Res. (1997) [Pubmed]
  22. 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]
  23. Neurotrophins rescue cerebellar granule neurons from oxidative stress-mediated apoptotic death: selective involvement of phosphatidylinositol 3-kinase and the mitogen-activated protein kinase pathway. Skaper, S.D., Floreani, M., Negro, A., Facci, L., Giusti, P. J. Neurochem. (1998) [Pubmed]
  24. A possible role for BDNF, NT-4 and TrkB in the spinal cord and muscle of rat subjected to mechanical overload, bupivacaine injection and axotomy. Sakuma, K., Watanabe, K., Sano, M., Uramoto, I., Nakano, H., Li, Y.J., Kaneda, S., Sorimachi, Y., Yoshimoto, K., Yasuhara, M., Totsuka, T. Brain Res. (2001) [Pubmed]
  25. Synergistic effects of brain-derived neurotrophic factor and ciliary neurotrophic factor on cultured basal forebrain cholinergic neurons from postnatal 2-week-old rats. Hashimoto, Y., Abiru, Y., Nishio, C., Hatanaka, H. Brain Res. Dev. Brain Res. (1999) [Pubmed]
  26. Influence of neurotrophic factors on morphine- and cocaine-induced biochemical changes in the mesolimbic dopamine system. Berhow, M.T., Russell, D.S., Terwilliger, R.Z., Beitner-Johnson, D., Self, D.W., Lindsay, R.M., Nestler, E.J. Neuroscience (1995) [Pubmed]
  27. Stimulation of GABAergic neuron differentiation by NT-4/5 in cultures of rat cerebral cortex. Widmer, H.R., Hefti, F. Brain Res. Dev. Brain Res. (1994) [Pubmed]
  28. Involvement of protease-activated receptor-1 in the in vitro development of mesencephalic dopaminergic neurons. Debeir, T., Benavides, J., Vigé, X. Neuroscience (1998) [Pubmed]
  29. NT-4/5 and LIF, but not NT-3 and BDNF, promote NPY mRNA expression in cortical neurons in the absence of spontaneous bioelectrical activity. Wirth, M.J., Obst, K., Wahle, P. Eur. J. Neurosci. (1998) [Pubmed]
  30. Neurotrophins regulate agrin-induced postsynaptic differentiation. Wells, D.G., McKechnie, B.A., Kelkar, S., Fallon, J.R. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  31. Effects of axotomy and intraocular administration of NT-4, NT-3, and brain-derived neurotrophic factor on the survival of adult rat retinal ganglion cells. A quantitative in vivo study. Peinado-Ramón, P., Salvador, M., Villegas-Pérez, M.P., Vidal-Sanz, M. Invest. Ophthalmol. Vis. Sci. (1996) [Pubmed]
  32. Effects of brain-derived neurotrophic factor and neurotrophin-4 on isolated cultured retinal ganglion cells: evaluation by flow cytometry. Kashiwagi, F., Kashiwagi, K., Iizuka, Y., Tsukahara, S. Invest. Ophthalmol. Vis. Sci. (2000) [Pubmed]
  33. Neurotrophin 4/5 is required for the normal development of the slow muscle fiber phenotype in the rat soleus. Carrasco, D.I., English, A.W. J. Exp. Biol. (2003) [Pubmed]
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