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What is the biological significance of BDNF mRNA targeting in the dendrites?

Clues from epilepsy and cortical development

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Abstract

The neurotrophin brain-derived neurotrophic factor (BDNF) is a regulatory factor of several, partially contrasting, aspects of the biology of neural cells, including survival, growth, differentiation, and cell death. Regulation of the local availability of BDNF at distinct subcellular domains such as the cell soma, dendrites, axons, and spines appears to be the key to conferring spatial and temporal specificity of the different effects elicited by this neurotrophin. This article reviews recent findings in the context of epileptogenesis and visual cortex maturation that showed that different BDNF messenger RNA (mRNA) transcripts are localized at different subcellular locations in hippocampal and cortical neurons. It also reviews findings demonstrating that strong depolarizing stimuli, both in vitro and in vivo, elicit accumulation of BDNF mRNA and protein in the distal dendrites through a signaling pathway involving the activation of the N-methyl-d-aspartate and tyrosine kinase B receptors and an intracellular increase in Ca2+ concentration. Finally, this article proposes that the regulation of the delivery of BDNF mRNA and protein to the different subcellular domains—particularly the dendritic compartment—may represent a fundamental aspect of the processes of cellular and synaptic morphological rearrangements underlying epileptogenesis and postnatal development of the visual cortex.

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References

  1. Barde Y. A., Edgar D., and Thoenen H. (1982) Purification of a new neurotrophic factor from mammalian brain. EMBO J. 1, 549–553.

    PubMed  CAS  Google Scholar 

  2. Leibrock J., Lottspeich F., Hohn A., et al. (1989) Molecular cloning and expression of brain-derived neurotrophic factor. Nature 341, 149–152.

    Article  PubMed  CAS  Google Scholar 

  3. Bibel M. and Barde Y. A. (2000) Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev. 14, 2919–2937.

    Article  PubMed  CAS  Google Scholar 

  4. Huang E. J. and Reichardt L. F. (2003) Trk receptors: roles in neuronal signal transduction. Annu. Rev. Biochem. 72, 609–642.

    Article  PubMed  CAS  Google Scholar 

  5. Casaccia-Bonnefil P., Gu C., and Chao M. V. (1999) Neurotrophins in cell survival/death decisions. Adv. Exp. Med. Biol. 468, 275–282.

    PubMed  CAS  Google Scholar 

  6. Lu B. (2003) Pro-region of neurotrophins: role in synaptic modulation. Neuron. 39, 735–738.

    Article  PubMed  CAS  Google Scholar 

  7. Schuman E. (1999) Neurotrophin regulation of synaptic transmission. Curr. Opin. Neurobiol. 9, 105–109.

    Article  PubMed  CAS  Google Scholar 

  8. Tanaka T., Saito H., and Matsuki N. (1997) Inhibition of GABAA synaptic responses by brain-derived neurotrophic factor (BDNF) in rat hippocampus. J. Neurosci. 17, 2959–2966.

    PubMed  CAS  Google Scholar 

  9. Kaplan D. R. and Miller F. D. (2000) Neurotrophin signal transduction in the nervous system. Curr. Opin. Neurobiol. 10, 381–391.

    Article  PubMed  CAS  Google Scholar 

  10. Thoenen H. (2000) Neurotrophins and activity-dependent plasticity. Prog. Brain Res. 128, 183–191.

    Article  PubMed  CAS  Google Scholar 

  11. Patapoutian A. and Reichardt L. F. (2001) Trk receptors: mediators of neurotrophin action. Curr. Opin. Neurobiol. 11, 272–280.

    Article  PubMed  CAS  Google Scholar 

  12. Heerssen H. M. and Segal R. A. (2002) Location, location, location: a spatial view of neurotrophin signal transduction. Trends Neurosci. 25, 160–165.

    Article  PubMed  CAS  Google Scholar 

  13. Palacios I. M. and St Johnston D. (2001) Getting the message across: the intracellular localization of mRNAs in higher eukaryotes. Annu. Rev. Cell Dev. Biol. 17, 569–614.

    Article  PubMed  CAS  Google Scholar 

  14. Steward O. (1997) mRNA localization in neurons: a multipurpose mechanism? Neuron 18, 9–12.

    Article  PubMed  CAS  Google Scholar 

  15. Steward O. and Schuman E. M. (2001) Protein synthesis at synaptic sites on dendrites. Annu. Rev. Neurosci. 24, 299–325.

    Article  PubMed  CAS  Google Scholar 

  16. Tiedge H., Bloom F. E., and Richter D. (1999) RNA, whither goest thou? Science 283, 186, 187.

    Article  PubMed  CAS  Google Scholar 

  17. Tiedge H. and Brosius J. (1996) Translational machinery in dendrites of hippocampal neurons in culture. J. Neurosci. 16, 7171–7181.

    PubMed  CAS  Google Scholar 

  18. Torre E. R. and Steward O. (1996) Protein synthesis within dendrites: glycosylation of newly synthesized proteins in dendrites of hippocampal neurons in culture. J. Neurosci. 16, 5967–5978.

    PubMed  CAS  Google Scholar 

  19. Steward O. and Reeves T. M. (1988) Protein-synthetic machinery beneath postsynaptic sites on CNS neurons: association between polyribosomes and other organelles at the synaptic site. J. Neurosci. 8, 176–184.

    PubMed  CAS  Google Scholar 

  20. Gardiol A., Racca C., and Triller A. (1999) Dendritic and postsynaptic protein synthetic machinery. J. Neurosci. 19, 168–179.

    PubMed  CAS  Google Scholar 

  21. Kuhl D. and Skehel P. (1998) Dendritic localization of mRNAs. Curr. Opin. Neurobiol. 8, 600–606.

    Article  PubMed  CAS  Google Scholar 

  22. Mohr E. (1999) Subcellular RNA compartmentalization. Prog. Neurobiol. 57, 507–525.

    Article  PubMed  CAS  Google Scholar 

  23. Eberwine J., Belt B., Kacharmina J. E., and Miyashiro K. (2002) Analysis of subcellularly localized mRNAs using in situ hybridization, mRNA amplification, and expression profiling. Neurochem Res. 27, 1065–1077.

    Article  PubMed  CAS  Google Scholar 

  24. Kang H. and Schuman E. M. (1996) A requirement for local protein synthesis in neurotrophin-induced hippocampal synaptic plasticity. Science 273, 1402–1406.

    Article  PubMed  CAS  Google Scholar 

  25. Van de Bor V. and Davis I. (2004) mRNA localization gets more complex. Curr. Opin. Cell Biol. 16, 300–307.

    Article  PubMed  CAS  Google Scholar 

  26. Wells D. G., Richter J. D., and Fallon J. R. (2000) Molecular mechanisms for activity-regulated protein synthesis in the synapto-dendritic compartment. Curr. Opin. Neurobiol. 10, 132–137.

    Article  PubMed  CAS  Google Scholar 

  27. Kindler S. and Monshausen M. (2002) Candidate RNA-binding proteins regulating extrasomatic mRNA targeting and translation in mammalian neurons. Mol. Neurobiol. 25, 149–165.

    Article  PubMed  CAS  Google Scholar 

  28. van Eeden F. and St Johnston D. (1999) The polarisation of the anterior-posterior and dorsal-ventral axes during Drosophila oogenesis. Curr. Opin. Genet. Dev. 9, 396–404.

    Article  PubMed  Google Scholar 

  29. Kiebler M. A., Hemraj I., Verkade P., et al. (1999) The mammalian staufen protein localizes to the somatodendritic domain of cultured hippocampal neurons: implications for its involvement in mRNA transport. J. Neurosci. 19, 288–297.

    PubMed  CAS  Google Scholar 

  30. Kohrmann M., Luo M., Kaether C., DesGroseillers L., Dotti C. G., and Kiebler M. A. (2001) Microtubule-dependent recruitment of Staufen-green fluorescent protein into large RNA-containing granules and subsequent dendritic transport in living hippocampal neurons. Mol. Biol. Cell 10, 2945–2953.

    Google Scholar 

  31. Tang S. J. and Schuman E. M. (2002) Protein synthesis in the dendrite. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 357, 521–529.

    Article  PubMed  CAS  Google Scholar 

  32. Davis L., Banker G. A., and Steward O. (1987) Selective dendritic transport of RNA in hippocampal neurons in culture. Nature 330, 477–479.

    Article  PubMed  CAS  Google Scholar 

  33. Severt W. L., Biber T. U., Wu X., Hecht N. B., DeLorenzo R. J., and Jakoi E. R. (1999) The suppression of testis-brain RNA binding protein and kinesin heavy chain disrupts mRNA sorting in dendrities. J. Cell Sci. 112, 3691–3702.

    PubMed  CAS  Google Scholar 

  34. Hoek K. S., Kidd G. J., Carson J. H., and Smith R. (1998) hnRNP A2 selectively binds the cytoplasmic transport sequence of myelin basic protein mRNA. Biochemistry 37, 7021–7029.

    Article  PubMed  CAS  Google Scholar 

  35. Mazroui R., Huot M. E., Tremblay S., Filion C., Labelle Y., and Khandjian E. W. (2002) Trapping of messenger RNA by Fragile X Mental Retardation protein into cytoplasmic granules induces translation repression. Hum. Mol. Genet. 11, 3007–3017.

    Article  PubMed  CAS  Google Scholar 

  36. Shan J. Munro T. P., Barbarese E., Carson J. H., and Smith R. (2003) A molecular mechanism for mRNA trafficking in neuronal dendrites. J. Neurosci. 23, 8859–8866.

    PubMed  CAS  Google Scholar 

  37. Anderson K. D., Merhege M. A., Morin M., Bolognani F., and Perrone-Bizzozero N. I. (2003) Increased expression and localization of the RNA-binding protein HuD and GAP-43 mRNA to cytoplasmic granules in DRG neurons during nerve regeneration. Exp. Neurol. 183, 100–108.

    Article  PubMed  CAS  Google Scholar 

  38. Tiruchinapalli D. M., Oleynikov Y., Kelic S., et al. (2003) Activity-dependent trafficking and dynamic localization of zipcode binding protein 1 and beta-actin mRNA in dendrites and spines of hippocampal neurons. J. Neurosci. 23, 3251–3261.

    PubMed  CAS  Google Scholar 

  39. Macchi P., Kroening S., Palacios I. M., et al. (2003) Barentsz, a new component of the Staufen-containing ribonucleoprotein particles in mammalian cells, interacts with Staufen in an RNA-dependent manner. J. Neurosci. 23, 5778–5788.

    PubMed  CAS  Google Scholar 

  40. Barbarese E., Koppel D. E., Deutscher M. P., et al. (1995) Protein translation components are colocalized in granules in oligodendrocytes. J. Cell Sci. 108, 2781–2790.

    PubMed  CAS  Google Scholar 

  41. Carson J. H., Kwon S., and Barbarese E. (1998) RNA trafficking in myelinating cells. Curr. Opin. Neurobiol. 8, 607–612.

    Article  PubMed  CAS  Google Scholar 

  42. Krichevsky A. M. and Kosik K. S. (2001) Neuronal RNA granules: a link between RNA localization and stimulation-dependent translation. Neuron 32, 683–696.

    Article  PubMed  CAS  Google Scholar 

  43. Kanai Y., Dohmae N., and Hirokawa N. (2004) Kinesin transports RNA: isolation and characterization of an RNA-transporting granule. Neuron 43, 513–525.

    Article  PubMed  CAS  Google Scholar 

  44. Tongiorgi E., Righi M., and Cattaneo A. (1997) Activity-dependent dendritic targeting of BDNF and TrkB mRNAs in hippocampal neurons. J. Neurosci. 17, 9492–9505.

    PubMed  CAS  Google Scholar 

  45. Righi M., Tongiorgi E., and Cattaneo A. (2000) Brain-derived neurotrophic factor (BDNF) induces dendritic targeting of BDNF and tyrosine kinase B mRNAs in hippocampal neurons through a phosphatidylinositol-3 kinase-dependent pathway. J. Neurosci. 20, 3165–3174.

    PubMed  CAS  Google Scholar 

  46. Tongiorgi E., Armellin M., Giulianini P. G., et al. (2004) BDNF mRNA and protein are targeted to discrete dendritic laminae by events that trigger epileptogenesis. J. Neurosci. 24, 6842–6852.

    Article  PubMed  CAS  Google Scholar 

  47. Job C. and Eberwine J. (2001) Identification of sites for exponential translation in living dendrites. Proc. Natl. Acad. Sci. USA 98, 13,037–13,042.

    Article  CAS  Google Scholar 

  48. Tongiorgi E., Armellin M., and Cattaneo A. (2000) Differential somato-dendritic localization of TrkA, TrkB, TrkC and p75 mRNAs in vivo. Neuroreport 11, 3265–3268.

    Article  PubMed  CAS  Google Scholar 

  49. McNamara J. O. (1999) Emerging insights into the genesis of epilepsy. Nature 399 (Suppl), A15-A22.

    PubMed  CAS  Google Scholar 

  50. Mody I. (1999) Synaptic plasticity in kindling. Adv. Neurol. 79, 631–643.

    PubMed  CAS  Google Scholar 

  51. Brooks-Kayal A. R., Shumate M. D., Jin H., Rikhter T. Y., and Coulter D. A. (1998) Selective changes in single cell GABA(A) receptor subunit expression and function in temporal lobe epilepsy. Nat. Med. 4, 1166–1172.

    Article  PubMed  CAS  Google Scholar 

  52. Ernfors P., Bengzon J., Kokaia Z., Persson H., and Lindvall O. (1991) Increased levels of messenger RNAs for neurotrophic factors in the brain during kindling epileptogenesis. Neuron 7, 165–176.

    Article  PubMed  CAS  Google Scholar 

  53. Isackson P. J., Huntsman M. M., Murray K. D., and Gall C. M. (1991) BDNF mRNA expression is increased in adult rat forebrain after limbic seizures: temporal patterns of induction distinct from NGF. Neuron 6, 937–948.

    Article  PubMed  CAS  Google Scholar 

  54. Bengzon J., Kokaia Z., Ernfors P., et al. (1993) Regulation of neurotrophin and trkA, trkB and trkC tyrosine kinase receptor messenger RNA expression in kindling. Neuroscience 53, 433–446.

    Article  PubMed  CAS  Google Scholar 

  55. Simonato, M., Molteni R., Bregola G., et al. (1998) Different patterns of induction of FGF-2, FGF-1 and BDNF mRNAs during kindling epielptogenesis in the rat. Eur. J. Neurosci. 10, 955–963.

    Article  PubMed  CAS  Google Scholar 

  56. Murray K. D., Isackson P. J., Eskin T. A., et al. (2000) Altered mRNA expression for brain-derived neurotrophic factor and type II calcium/calmodulin-dependent protein kinase in the hippocampus of patients with intractable temporal lobe epilepsy. J. Comp. Neurol. 418, 411–422.

    Article  PubMed  CAS  Google Scholar 

  57. Huang Y., Doherty J. J., and Dingledine R. (2002) Altered histone acetylation at glutamate receptor 2 and brain-derived neurotrophic factor genes is an early event triggered by status epilepticus. J. Neurosci. 22, 8422–8428.

    PubMed  CAS  Google Scholar 

  58. Binder D. K., Routbort M. J., and McNamara J. O. (1999) Immunohistochemical evidence of seizure-induced activation of trk receptors in the mossy fiber pathway of adult rat hippocampus. J. Neurosci. 19, 4616–4626.

    PubMed  CAS  Google Scholar 

  59. Kokaia M., Ernfors P., Kokaia Z., Elmer E., Jaenisch R., and Lindvall O. (1995) Suppressed epileptogenesis in BDNF mutant mice. Exp. Neurol. 133, 215–224.

    Article  PubMed  CAS  Google Scholar 

  60. Binder D. K., Routbort M., Ryan T. E., Yancopoulos D. G., and McNamara J. O. (1999b) Selective inhibition of kindling development by intraventricular administration of TrkB receptor body. J. Neurosci. 19, 1424–1436.

    PubMed  CAS  Google Scholar 

  61. Lahteinen S., Pitkanen A., Saarelainen T., Nissinen J., Koponen E., and Castren E. (2002) Decreased BDNF signalling in transgenic mice reduces epileptogenesis. Eur. J. Neurosci. 15, 721–734.

    Article  PubMed  Google Scholar 

  62. Croll S. D., Suri C., Compton D. L., et al. (1999) Brain-derived neurotrophic factor transgenic mice exhibit passive avoidance deficits, increased seizure severity and in vitro hyper-excitability in the hippocampus and entorhinal cortex. Neuroscience 93, 1491–1506.

    Article  PubMed  CAS  Google Scholar 

  63. Xu B., Michalski B., Racine R. J., and Fahnestock M. (2004) The effects of brain-derived neurotrophic factor (BDNF) administration on kindling induction, Trk expression and seizure-related morphological changes. Neuroscience 126, 521–531.

    Article  PubMed  CAS  Google Scholar 

  64. He X. P., Kotloski R., Nef S., Luikart B. W., Parada L. F., and McNamara J. O. (2004) Conditional deletion of TrkB but not BDNF prevents epileptogenesis in the kindling model. Neuron 43, 31–42.

    Article  PubMed  CAS  Google Scholar 

  65. Schinder A. F. and Poo M. (2000) The neurotrophin hypothesis for synaptic plasticity. Trends Neurosci. 23, 639–645.

    Article  PubMed  CAS  Google Scholar 

  66. Korte M., Minichiello L., Klein R., and Bonhoeffer T. 2000) Shc-binding site in the TrkB receptor is not required for hippocampal long-term potentiation. Neuropharmacology 39, 717–724.

    Article  PubMed  CAS  Google Scholar 

  67. He X. P., Minichiello L., Klein R., and McNamara, J. O. (2002) Immunohistochemical evidence dence of seizure-induced activation of trkB receptors in the mossy fiber pathway of adult mouse hippocampus. J. Neurosci. 22, 7502–7508.

    PubMed  CAS  Google Scholar 

  68. Zhou X. F. and Rush R. A. (1996) Endogenous brain-derived neurotrophic factor is anterogradely transported in primary sensory neurons. Neuroscience 74, 945–953.

    PubMed  CAS  Google Scholar 

  69. Conner J. M., Lauterborn J. C., Yan Q., Gall C. M., and Varon S. (1997) Distribution of brain-derived neurotrophic factor (BDNF) protein and mRNA in the normal adult rat CNS: evidence for anterograde axonal transport. J. Neurosci. 17, 2295–2313.

    PubMed  CAS  Google Scholar 

  70. Smith M. A., Zhang L. X., Lyons W. E., and Mamounas L. A. (1997) Anterograde transport of endogenous brain-derived neurotrophic factor in hippocampal mossy fibers. Neuroreport 8, 1829–1834.

    Article  PubMed  CAS  Google Scholar 

  71. Fawcett J. P., Bamji S. X., Causing C. G., et al. (1998) Functional evidence that BDNF is an anterograde neuronal trophic factor in the CNS. J. Neurosci. 18, 2808–2821.

    PubMed  CAS  Google Scholar 

  72. Elmer E., Kokaia Z., Kokaia M., Carnahan J., Nawa H., and Lindvall O. (1998) Dynamic changes of brain-derived neurotrophic factor protein levels in the rat forebrain after single and recurring kindling-induced seizures. Neuroscience 83, 351–362.

    Article  PubMed  CAS  Google Scholar 

  73. Altar C. A. and Di Stefano P. S. (1998) Neurotrophin trafficking by anterograde transport. Trends Neurosci. 21, 433–437.

    Article  PubMed  CAS  Google Scholar 

  74. Simonato M., Bregola G., Armellin M., et al. (2002) Dendritic targeting of mRNAs for plasticity genes in experimental models of temporal lobe epilepsy. Epilepsia 43(Suppl), 153–158.

    Article  PubMed  CAS  Google Scholar 

  75. Merlio J. P., Ernfors P., Kokaia Z., et al. (1993) Increased production of the TrkB protein tyrosine kinase receptor after brain insults. Neuron 10, 151–64.

    Article  PubMed  CAS  Google Scholar 

  76. Wetmore C., Olson L., and Bean A. J. (1994) Regulation of brain-derived neurotrophic factor (BDNF) expression and release from hippocampal neurons is mediated by non-NMDA type glutamate receptors. J. Neurosci. 14, 1688–1700.

    PubMed  CAS  Google Scholar 

  77. Zafra F., Hengerer B., Leibrock J., Thoenen H., and Lindholm D. (1990) Activity dependent regulation of BDNF and NGF mRNAs in the rat hippocampus is mediated by non-NMDA glutamate receptors. EMBO J. 9, 3545–3550.

    PubMed  CAS  Google Scholar 

  78. McNamara J. O., Russell R. D., Rigsbee L., and Bonhaus D. W. (1988) Anticonvulsant and antiepileptogenic actions of MK-801 in the kindling and electroshock models. Neuropharmacology 27, 563–568.

    Article  PubMed  CAS  Google Scholar 

  79. Ormandy G. C., Jope R. S., and Snead O. C. 3rd (1989) Anticonvulsant actions of MK-801 on the lithium-pilocarpine model of status epilepticus in rats. Exp. Neurol. 106, 172–180.

    Article  PubMed  CAS  Google Scholar 

  80. Rice A. C. and DeLorenzo R. J. (1998) NMDA receptor activation during status epilepticus is required for the development of epilepsy. Brain Res. 782, 240–247.

    Article  PubMed  CAS  Google Scholar 

  81. Vezzani A., Ravizza T., Moneta D., et al. (1999) Brain-derived neurotrophic factor immunore-activity in the limbic system of rats after acute seizures and during spontaneous convulsions: temporal evolution of changes as compared to Neuropeptide Y. Neuroscience 90, 1445–1461.

    Article  PubMed  CAS  Google Scholar 

  82. Kryl D., Yacoubian T., Haapasalo A., Castren E., Lo D., and Barker P. A. (1999) Subcellular localization of full-length and truncated Trk receptor isoforms in polarized neurons and epithelial cells. J. Neurosci. 19, 5823–5833.

    PubMed  CAS  Google Scholar 

  83. Goutan E., Marti E., and Ferrer I. (1998) BDNF, and full length and truncated TrkB expression in the hippocampus of the rat following kainic acid excitotoxic damage. Evidence of complex time-dependent and cell-specific responses. Brain Res. Mol. Brain Res. 59, 154–164.

    Article  PubMed  CAS  Google Scholar 

  84. Drake C. T., Milner T. A., and Patterson S. L. (1999) Ultrastructural localization of full-length trkB immunoreactivity in rat hippocampus suggests multiple roles in modulating activity-dependent synaptic plasticity. J. Neurosci. 19, 8009–8026.

    PubMed  CAS  Google Scholar 

  85. Bhattacharyya A., Watson F. L., Bradlee T. A., Pomeroy S. L, Stiles C. D., and Segal R. A. (1997) Trk receptors function as rapid retrograde signal carriers in the adult nervous system. J. Neurosci. 17, 7007–7016.

    PubMed  CAS  Google Scholar 

  86. Lessmann V. and Heumann R. (1998) Modulation of unitary glutamatergic synapses by neurotrophin-4/5 or brain-derived neurotrophic factor in hippocampal microcultures: presynaptic enhancement depends on pre-estab lished paired-pulse facilitation. Neuroscience 86, 399–413.

    Article  PubMed  CAS  Google Scholar 

  87. Schinder A. F., Berninger B., and Poo M. (2000) Postsynaptic target specificity of neurotrophin-induced presynaptic potentiation. Neuron 25, 151–163.

    Article  PubMed  CAS  Google Scholar 

  88. Wardle R. A. and Poo M. M. (2003) Brain-derived neurotrophic factor modulation of GABA ergic synapses by postsynaptic regulation of chloride transport. J. Neurosci. 23, 8722–8732.

    PubMed  CAS  Google Scholar 

  89. Kang H. and Schuman E. M. (1995a) Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus. Science 267, 1658–1662.

    Article  PubMed  CAS  Google Scholar 

  90. Kang H. and Schuman E. M. (1995b) Neurotrophin-induced modulation of synaptic transmission in the adult hippocampus. J. Physiol. Paris 89, 11–22.

    Article  PubMed  CAS  Google Scholar 

  91. Kang H., Welcher A. A., Shelton D., and Schuman E. M. (1997) Neurotrophins and time: different roles for TrkB signaling in hippocampal long-term potentiation. Neuron 19, 653–664.

    Article  PubMed  CAS  Google Scholar 

  92. Messaoudi E., Bardsen K., Srebro B., and Bramham C. R. (1998) Acute intrahippocampal infusion of BDNF induces lasting potentiation of synaptic transmission in the rat dentate gyrus. J. Neurophysiol. 79, 496–499.

    PubMed  CAS  Google Scholar 

  93. Tanaka T., Saito H., and Matsuki N. (1997) Inhibition of GABAA synaptic responses by brain-derived neurotrophic factor (BDNF) in rat hippocampus. J. Neurosci. 17, 2959–2966.

    PubMed  CAS  Google Scholar 

  94. Frerking M., Malenka R. C., and Nicoll R. A. (1998) Brain-derived neurotrophic factor (BDNF) modulates inhibitory, but not excitatory, transmission in the CA1 region of the hippocampus. J. Neurophysiol. 80, 3383–3386.

    PubMed  CAS  Google Scholar 

  95. Figurov A., Pozzo-Miller L. D., Olafsson P., Wang T., and Lu B. (1996) Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus. Nature 381, 706–709.

    Article  PubMed  CAS  Google Scholar 

  96. Gottschalk W., Pozzo-Miller L. D., Figurov A., and Lu B. (1998) Presynaptic modulation of synaptic transmission and plasticity by brain-derived neurotrophic factor in the developing hippocampus. J. Neurosci. 18, 6830–6839.

    PubMed  CAS  Google Scholar 

  97. Patterson S. L., Abel T., Deuel T. A., Martin K. C., Rose J. C., and Kandel E. R. (1996) Recombinant BDNF rescues deficits in basal synaptic transmission and hippocampal LTP in BDNF knockout mice. Neuron 16, 1137–1145.

    Article  PubMed  CAS  Google Scholar 

  98. Berninger B., Schinder A. F., and Poo M. M. (1999) Synaptic reliability correlates with reduced susceptibility to synaptic potentiation by brain-derived neurotrophic factor. Learn Mem. 6, 232–242.

    PubMed  CAS  Google Scholar 

  99. Kafitz K. W., Rose C. R., Thoenen H., and Konnerth A. (1999) Neurotrophin-evoked rapid excitation through TrkB receptors. Nature 401, 918–921.

    Article  PubMed  CAS  Google Scholar 

  100. Lohof A. M., Ip N. Y., and Poo M. M. (1993) Potentiation of developing neuromuscular synapses by the neurotrophins NT-3 and BDNF. Nature 363, 350–353.

    Article  PubMed  CAS  Google Scholar 

  101. Takei N., Sasaoka K., Inoue K., Takahashi M., Endo Y., and Hatanaka H. (1997) Brain-derived neurotrophic factor increases the stimulation-evoked release of glutamate and the levels of exocytosis-associated proteins in cultured cortical neurons from embryonic rats. J. Neurochem. 68, 370–375.

    PubMed  CAS  Google Scholar 

  102. Takei N., Numakawa T., Kozaki S., et al. (1998) Brain-derived neurotrophic factor induces rapid and transient release of glutamate through the non-exocytotic pathway from cortical neurons. J. Biol. Chem. 273, 27,620–27,624.

    CAS  Google Scholar 

  103. Li Y. X., Zhang Y., Lester H. A., Schuman E. M., and Davidson N. (1998) Enhancement of neurotransmitter release induced by brain-derived neurotrophic factor in cultured hippocampal neurons. J. Neurosci. 18, 10,231–10,240.

    CAS  Google Scholar 

  104. Levine E. S., Crozier R. A., Black I. B., and Plummer M. R. (1998) Brain-derived neurotrophic factor modulates hippocampal synaptic transmission by increasing N-methyl-D-aspartic acid receptor activity. Proc. Natl. Acad. Sci. USA 95, 10,235–10,239.

    Article  CAS  Google Scholar 

  105. Suen P. C., Wu K., Levine E. S., et al. (1997) Brain-derived neurotrophic factor rapidly enhances phosphorylation of the postsynaptic N-methyl-D-aspartate receptor subunit 1. Proc. Natl. Acad. Sci. USA 94, 8191–8195.

    Article  PubMed  CAS  Google Scholar 

  106. Brunig I., Penschuck S., Berninger B., Benson J., and Fritschy J. M. (2001) BDNF reduces miniature inhibitory postsynaptic currents by rapid downregulation of GABA(A) receptor surface expression. Eur. J. Neurosci. 13, 1320–1328.

    Article  PubMed  CAS  Google Scholar 

  107. Scharfman H. E. (1997) Hyperexcitability in combined entorhinal/hippocampal slices of adult rat after exposure to brain-derived neurotrophic factor. J. Neurophysiol. 78, 1082–1095.

    PubMed  CAS  Google Scholar 

  108. Scharfman H. E., Goodman J. H., and Sollas A. L. (1999) Actions of brain-derived neurotrophic factor in slices from rats with spontaneous seizures and mossy fiber sprouting in the dentate gyrus. J. Neurosci. 19, 5619–5631.

    PubMed  CAS  Google Scholar 

  109. Binder D. K., Croll S. D., Gall C. M., and Scharfman H. E. (2001) BDNF and epilepsy: too much of a good thing? Trends Neurosci. 24, 47–53.

    Article  PubMed  CAS  Google Scholar 

  110. King G. L., Dingledine R., Giacchino J. L., and McNamara J. O. (1985) Abnormal neuronal excitability in hippocampal slices from kindled rats. J. Neurophysiol. 54, 1295–1304.

    PubMed  CAS  Google Scholar 

  111. Egan M. F., Kojima M., Callicott J. H., et al. (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112, 257–269.

    Article  PubMed  CAS  Google Scholar 

  112. Chen Z. Y., Patel P. D., Sant G., et al. (2004) Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J. Neurosci. 24, 4401–4411.

    Article  PubMed  CAS  Google Scholar 

  113. Kanemoto K., Kawasaki J., Tarao Y., et al. (2003) Association of partial epilepsy with brain-derived neurotrophic factor (BDNF) gene polymorphisms. Epilepsy Res. 53, 255–258.

    Article  PubMed  CAS  Google Scholar 

  114. Chou I. C., Tsai C. H., Lee C. C., Lin S. S., and Tsai F. J. (2004) Brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms in febrile seizures. Epilepsy Res. 60, 27–29.

    Article  PubMed  CAS  Google Scholar 

  115. Liu Q. R., Walther D., Drgon T., et al. (2005) Human brain derived neurotrophic factor (BDNF) genes, splicing patterns and assessments of associations with substance abuse and Parkinson's disease. Am. J. Med. Gen. Part B (Neuropsych. Gen.) 134, 93–103.

    Article  Google Scholar 

  116. Pinkstaff J. K., Chappell S. A., Mauro V. P., Edelman G. M., and Krushel L. A. (2001) Internal initiation of translation of five dendritically localized neuronal mRNAs. Proc. Natl. Acad. Sci. USA 98, 2770–2775.

    Article  PubMed  CAS  Google Scholar 

  117. Zaitsev E. and Lu B. (2003) CAP-independent translation of BDNF: IRES activity of two BDNF RNA transcripts. Soc. Neurosci. Abstr. 334.5.

  118. Wiesel T. N. and Hubel D. H. (1963) Single cell responses in striate cortex of kittens deprived of vision in one eye. J. Neurophysiol. 26, 1003–1017.

    PubMed  CAS  Google Scholar 

  119. Hubel D. H., Wiesel T. N., and LeVay S. (1977) Plasticity of ocular dominance columns in monkey striate cortex. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 278, 377–409.

    PubMed  CAS  Google Scholar 

  120. Shatz C. J. and Stryker M. P. (1978) Ocular dominance in layer IV of the cat's visual cortex and the effects of monocular deprivation. J. Physiol. 281, 267–283.

    PubMed  CAS  Google Scholar 

  121. Kohara K., Kitamura A., Adachi N., et al. (2003) Inhibitory but not excitatory cortical neurons require presynaptic brain-derived neurotrophic factor for dendritic development, as revealed by chimera cell culture. J. Neurosci. 23, 6123–6131.

    PubMed  CAS  Google Scholar 

  122. Jin X., Hu H., Mathers P. H., and Agmon A. (2003) Brain-derived neurotrophic factor mediates activity-dependent dendritic growth in nonpyramidal neocortical interneurons in developing organotypic cultures. J. Neurosci. 23, 5662–5673.

    PubMed  CAS  Google Scholar 

  123. McAllister A. K., Katz L. C., and Lo D. C. (1996) Neurotrophin regulation of cortical dendritic growth requires activity. Neuron 17, 1057–1064.

    Article  PubMed  CAS  Google Scholar 

  124. Horch H. W., Kruttgen A., Portbury S. D., and Katz L. C. (1999) Destabilization of cortical dendrites and spines by BDNF. Neuron 23, 353–364.

    Article  PubMed  CAS  Google Scholar 

  125. Sermasi E., Tropea D., and Domenici L. (1999) A new form of synaptic plasticity is transiently expressed in the developing rat visual cortex: a modulatory role for visual experience and BDNF. Neuroscience 91, 163–173.

    Article  PubMed  CAS  Google Scholar 

  126. Cabelli R. J., Hohn A., and Shatz C. J. (1995) Inhibition of ocular dominance column formation by infusion of NT-4/5 or BDNF. Science 267, 1662–1666.

    Article  PubMed  CAS  Google Scholar 

  127. Hata Y., Ohshima M., Ichisaka S., Wakita M., Fukuda M., and Tsumoto T. (2000) Brain-derived neurotrophic factor expands ocular dominance columns in visual cortex in monocularly deprived and nondeprived kittens but does not in adult cats. J. Neurosci. 20, RC57.

    Google Scholar 

  128. Lodovichi C., Berardi N., Pizzorusso T., and Maffei L. (2000) Effects of neurotrophins on cortical plasticity: same or different?. J. Neurosci. 20, 2155–2165.

    PubMed  CAS  Google Scholar 

  129. Huang Z. J., Kirkwood A., Pizzorusso T., et al. (1999). BDNF regulates the maturation of inhibition and the critical period of plasticity in mouse visual cortex. Cell 98, 739–755.

    Article  PubMed  CAS  Google Scholar 

  130. Gianfranceschi L., Siciliano R., Walls J., et al. (2003) Visual cortex is rescued from the effects of dark rearing by overexpression of BDNF. Proc. Natl. Acad. Sci. U S A. 100, 12,486–12,491.

    Article  CAS  Google Scholar 

  131. Carmignoto G., Pizzorusso T., Tia S., and Vicini S. (1997) Brain-derived neurotrophic factor and nerve growth factor potentiate excitatory synaptic transmission in the rat visual cortex. J. Physiol. 498, 153–164.

    PubMed  CAS  Google Scholar 

  132. Akaneya Y., Tsumoto T., Kinoshita S., and Hatanaka H. (1997) Brain-derived neurotrophic factor enhances long-term potentiation in rat visual cortex. J. Neurosci. 17, 6707–6716.

    PubMed  CAS  Google Scholar 

  133. Sermasi E., Margotti E., Cattaneo A., and Domenici L. (2000) TrkB signalling controls LTP but not LTD in the developing rat visual cortex. Eur. J. Neurosci. 12, 1411–1419.

    Article  PubMed  CAS  Google Scholar 

  134. Kinoshita S., Yasuda H., Taniguchi N., Katoh-Semba R., Hatanaka H., and Tsumoto (1999) T. Brain-Derived Neurotrophic Factor Prevents Low-Frequency Inputs from Inducing Long-Term Depression in the Developing Visual Cortex. J. Neurosci. 19, 2122–2130.

    PubMed  CAS  Google Scholar 

  135. Jiang B., Akaneya Y., Hata Y., and Tsumoto T. (2003) Long-term depression is not induced by low-frequency stimulation in rat visual cortex in vivo: a possible preventing role of endogenous brain-derived neurotrophic factor. J. Neurosci. 23, 3761–3770.

    PubMed  CAS  Google Scholar 

  136. Capsoni, S., Tongiorgi E., Cattaneo A., and Domenici L. (1999) Dark rearing blocks the developmental down-regulation of brain-drived neurotrophic factor messenger RNA expression in layers IV and V of the rat visual cortex. Neuroscience 88, 393–403.

    Article  PubMed  CAS  Google Scholar 

  137. Capsoni S., Tongiorgi E., Cattaneo A., and Domenici L. (1999) Differential regulation of brain-derived neurotrophic factor mRNA cellular expression in the adult rat visual cortex. Neuroscience 93, 1033–1040.

    Article  PubMed  CAS  Google Scholar 

  138. Pattabiraman P. P., Tropea D., Chiaruttini C., Tongiorgi E., Cattaneo A., and Domenici L. (2005) Neuronal activity regulates the developmental expression and subcellular localization of cortical BDNF mRNA isoforms in vivo Mol. Cell. Neurosci. 28, 556–570.

    Article  PubMed  CAS  Google Scholar 

  139. Tropea D., Capsoni S., Tongiorgi E., Giannotta S., Cattaneo A., and Domenici L. (2001) Mis-match between BDNF mRNA and protein expression in the developing visual cortex. Role of visual experience. Eur. J. Neurosci. 13, 709–721.

    Article  PubMed  CAS  Google Scholar 

  140. Wu L., Wells D., Tay J., Medis, D., et al. (1998) CPEB-mediated cytoplasmic polyadenylation and the regulation of experience-dependent translation of alpha-CaMKII mRNA at synapses. Neuron 21, 1129–1139.

    Article  PubMed  CAS  Google Scholar 

  141. Timmusk T., Palm K., Metsis M., et al. (1993) Multiple promoters direct tissue-specific expression of the rat BDNF gene. Neuron 10, 475–489.

    Article  PubMed  CAS  Google Scholar 

  142. Metsis M., Timmusk, T., Arenas E., and Persson H. (1993) Differential usage of multiple brain-derived neurotrophic factor promoters in the rat brain following neuronal activation. Proc Natl Acad Sci USA 90, 8802–8806.

    Article  PubMed  CAS  Google Scholar 

  143. Kokaia Z., Metsis M., Kokaia M., et al. (1994) Brain insults in rats induce increased expression of the BDNF gene through differential use of multiple promoters. Eur. J. Neurosci. 6, 587–596.

    Article  PubMed  CAS  Google Scholar 

  144. Timmusk T., Belluardo N., Persson H., and Metsis M. (1994) Analysis of transcriptional initiation and translatability of brain-derived neurotrophic factor mRNAs in the rat brain. Neuroscience 60, 287–291.

    Article  PubMed  CAS  Google Scholar 

  145. Hendry S. H., Jones E. G., DeFelipe J., Schmechel D., Brandon C., and Emson P. C. (1984) Neuropeptide-containing neurons of the cerebral cortex are also GABAergic. Proc. Natl. Acad. Sci. USA 81, 6526–6530.

    Article  PubMed  CAS  Google Scholar 

  146. Gonchar Y. and Burkhalter A. (1997) Three distinct families of GABAergic neurons in rat visual cortex. Cereb. Cortex 7, 347–358.

    Article  PubMed  CAS  Google Scholar 

  147. Gupta A., Wang Y., and Markram H. (2000) Organizing principles for a diversity of GABAergic interneurons and synapses in the neocortex. Science 287, 273–278

    Article  PubMed  CAS  Google Scholar 

  148. Cellerino A., Maffei L., and Domenici L. (1996) The distribution of brain derived neurotrophic factor and its receptor trkB in parvalbumin containing neurons of the rat visual cortex. Eur. J. Neurosci. 6, 100–108.

    Google Scholar 

  149. Schmidt-Kastner R., Wetmore C., and Olson L. (1996) Comparative study of brain-derived neurotrophic factor messenger RNA and protein at the cellular level suggests multiple roles in hippocampus, striatum and cortex. Neuroscience 74, 161–183.

    Article  PubMed  CAS  Google Scholar 

  150. Horch H. W. and Katz L. C. (2002) BDNF release from single cells elicits local dendritic growth in nearby neurons. Nat. Neurosci. 5, 1177–1184.

    Article  PubMed  CAS  Google Scholar 

  151. Righi M., Tongiorgi E., and Cattaneo A. (2000) Brain-derived neurotrophic factor (BDNF) induces dendritic targeting of BDNF and tyrosine kinase B mRNAs in hippocampal neurons through a phosphatidylinositol-3 kinase-dependent pathway. J. Neurosci. 20, 3165–3174.

    PubMed  CAS  Google Scholar 

  152. Kang H. J. and Schuman E. M. (1996) A requirement for local protein synthesis in neurotrophin-induced hippocampal synaptic plasticity. Science 273, 1402–1406.

    Article  PubMed  CAS  Google Scholar 

  153. Aakalu G., Smith W. B., Nguyen N., Jiang C., and Schuman E. M. (2001) Dynamic visualization of local protein synthesis in hippocampal neurons. Neuron 30, 489–502.

    Article  PubMed  CAS  Google Scholar 

  154. Takei N., Inamura N., Kawamura M., et al. (2004) Brain-derived neurotrophic factor induces mammalian target of rapamycin dependent local activation of translation machinery and protein synthesis in neuronal dendrites. J. Neurosci. 24, 9760–9769.

    Article  PubMed  CAS  Google Scholar 

  155. Smart F. M., Edelman G. M., and Vanderklish P. W. (2003) BDNF induces translocation of initiation factor 4E to mRNA granules: evidence for a role of synaptic microfilaments and integrins. Proc. Natl. Acad. Sci. USA 100, 14,403–14,408.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. BRAIN Centre for Neuroscience Department of Biology, University of Trieste, Trieste, Italy

    Enrico Tongiorgi

  2. Institute of Neuroscience (CNR), Pisa, Italy

    Luciano Domenici

  3. International School for Advanced Studies (SISSA), Trieste, Italy

    Luciano Domenici

  4. Section of Pharmacology, Department of Clinical and Experimental Medicine, University of Ferrara, Ferrara, Italy

    Michele Simonato

  5. Neuroscience Center, University of Ferrara, Ferrara, Italy

    Michele Simonato

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  1. Enrico Tongiorgi
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  2. Luciano Domenici
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  3. Michele Simonato
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Correspondence to Enrico Tongiorgi.

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Tongiorgi, E., Domenici, L. & Simonato, M. What is the biological significance of BDNF mRNA targeting in the dendrites?. Mol Neurobiol 33, 17–32 (2006). https://doi.org/10.1385/MN:33:1:017

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