Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1995 Jan 1;128(1):185–199. doi: 10.1083/jcb.128.1.185

Identification of brain-derived neurotrophic factor promoter regions mediating tissue-specific, axotomy-, and neuronal activity-induced expression in transgenic mice

PMCID: PMC2120326  PMID: 7822414

Abstract

The structure of rat brain-derived neurotrophic factor (BDNF) gene is complex; four 5' exons are linked to separate promoters and one 3' exon is encoding the BDNF protein. To analyze the relative importance of the regulatory regions in vivo, we have generated transgenic mice with six different promoter constructs of the BDNF gene fused to the chloramphenicol acetyl transferase reporter gene. High level and neuronal expression of the reporter gene, that in many respects recapitulated BDNF gene expression, was achieved by using 9 kb of genomic sequences covering the promoter regions that lie adjacent to each other in the genome (promoters I and II and promoters III and IV, respectively) and by including sequences of BDNF intron-exon splice junctions and 3' untranslated region in the constructs. The genomic regions responsible for the in vivo upregulation of BDNF expression in the axotomized sciatic nerve and in the brain after kainic acid-induced seizures and KCl-induced spreading depression were mapped. These data show that regulation of the different aspects of BDNF expression is controlled by different regions in vivo, and they suggest that these promoter constructs may be useful for targeted expression of heterologous genes to specific regions of the central and peripheral nervous systems in an inducible manner.

Full Text

The Full Text of this article is available as a PDF (3.7 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alderson R. F., Alterman A. L., Barde Y. A., Lindsay R. M. Brain-derived neurotrophic factor increases survival and differentiated functions of rat septal cholinergic neurons in culture. Neuron. 1990 Sep;5(3):297–306. doi: 10.1016/0896-6273(90)90166-d. [DOI] [PubMed] [Google Scholar]
  2. Ang H. L., Carter D. A., Murphy D. Neuron-specific expression and physiological regulation of bovine vasopressin transgenes in mice. EMBO J. 1993 Jun;12(6):2397–2409. doi: 10.1002/j.1460-2075.1993.tb05894.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bading H., Ginty D. D., Greenberg M. E. Regulation of gene expression in hippocampal neurons by distinct calcium signaling pathways. Science. 1993 Apr 9;260(5105):181–186. doi: 10.1126/science.8097060. [DOI] [PubMed] [Google Scholar]
  4. Ballarín M., Ernfors P., Lindefors N., Persson H. Hippocampal damage and kainic acid injection induce a rapid increase in mRNA for BDNF and NGF in the rat brain. Exp Neurol. 1991 Oct;114(1):35–43. doi: 10.1016/0014-4886(91)90082-n. [DOI] [PubMed] [Google Scholar]
  5. Barde Y. A., Edgar D., Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO J. 1982;1(5):549–553. doi: 10.1002/j.1460-2075.1982.tb01207.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Beaudet L., Charron G., Houle D., Tretjakoff I., Peterson A., Julien J. P. Intragenic regulatory elements contribute to transcriptional control of the neurofilament light gene. Gene. 1992 Jul 15;116(2):205–214. doi: 10.1016/0378-1119(92)90517-s. [DOI] [PubMed] [Google Scholar]
  7. Belecky-Adams T., Wight D. C., Kopchick J. J., Parysek L. M. Intragenic sequences are required for cell type-specific and injury-induced expression of the rat peripherin gene. J Neurosci. 1993 Dec;13(12):5056–5065. doi: 10.1523/JNEUROSCI.13-12-05056.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brinster R. L., Allen J. M., Behringer R. R., Gelinas R. E., Palmiter R. D. Introns increase transcriptional efficiency in transgenic mice. Proc Natl Acad Sci U S A. 1988 Feb;85(3):836–840. doi: 10.1073/pnas.85.3.836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Castrén E., Pitkänen M., Sirviö J., Parsadanian A., Lindholm D., Thoenen H., Riekkinen P. J. The induction of LTP increases BDNF and NGF mRNA but decreases NT-3 mRNA in the dentate gyrus. Neuroreport. 1993 Jul;4(7):895–898. doi: 10.1097/00001756-199307000-00014. [DOI] [PubMed] [Google Scholar]
  10. Castrén E., Zafra F., Thoenen H., Lindholm D. Light regulates expression of brain-derived neurotrophic factor mRNA in rat visual cortex. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9444–9448. doi: 10.1073/pnas.89.20.9444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Choi T., Huang M., Gorman C., Jaenisch R. A generic intron increases gene expression in transgenic mice. Mol Cell Biol. 1991 Jun;11(6):3070–3074. doi: 10.1128/mcb.11.6.3070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Comelli M. C., Guidolin D., Seren M. S., Zanoni R., Canella R., Rubini R., Manev H. Time course, localization and pharmacological modulation of immediate early inducible genes, brain-derived neurotrophic factor and trkB messenger RNAs in the rat brain following photochemical stroke. Neuroscience. 1993 Jul;55(2):473–490. doi: 10.1016/0306-4522(93)90517-j. [DOI] [PubMed] [Google Scholar]
  13. Dugich-Djordjevic M. M., Tocco G., Lapchak P. A., Pasinetti G. M., Najm I., Baudry M., Hefti F. Regionally specific and rapid increases in brain-derived neurotrophic factor messenger RNA in the adult rat brain following seizures induced by systemic administration of kainic acid. Neuroscience. 1992;47(2):303–315. doi: 10.1016/0306-4522(92)90246-x. [DOI] [PubMed] [Google Scholar]
  14. Dugich-Djordjevic M. M., Tocco G., Willoughby D. A., Najm I., Pasinetti G., Thompson R. F., Baudry M., Lapchak P. A., Hefti F. BDNF mRNA expression in the developing rat brain following kainic acid-induced seizure activity. Neuron. 1992 Jun;8(6):1127–1138. doi: 10.1016/0896-6273(92)90133-x. [DOI] [PubMed] [Google Scholar]
  15. Ernfors P., Bengzon J., Kokaia Z., Persson H., Lindvall O. Increased levels of messenger RNAs for neurotrophic factors in the brain during kindling epileptogenesis. Neuron. 1991 Jul;7(1):165–176. doi: 10.1016/0896-6273(91)90084-d. [DOI] [PubMed] [Google Scholar]
  16. Ernfors P., Ibáez C. F., Ebendal T., Olson L., Persson H. Molecular cloning and neurotrophic activities of a protein with structural similarities to nerve growth factor: developmental and topographical expression in the brain. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5454–5458. doi: 10.1073/pnas.87.14.5454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ernfors P., Lee K. F., Jaenisch R. Mice lacking brain-derived neurotrophic factor develop with sensory deficits. Nature. 1994 Mar 10;368(6467):147–150. doi: 10.1038/368147a0. [DOI] [PubMed] [Google Scholar]
  18. Ernfors P., Wetmore C., Olson L., Persson H. Identification of cells in rat brain and peripheral tissues expressing mRNA for members of the nerve growth factor family. Neuron. 1990 Oct;5(4):511–526. doi: 10.1016/0896-6273(90)90090-3. [DOI] [PubMed] [Google Scholar]
  19. Evans T., Felsenfeld G., Reitman M. Control of globin gene transcription. Annu Rev Cell Biol. 1990;6:95–124. doi: 10.1146/annurev.cb.06.110190.000523. [DOI] [PubMed] [Google Scholar]
  20. Falkenberg T., Metsis M., Timmusk T., Lindefors N. Entorhinal cortex regulation of multiple brain-derived neurotrophic factor promoters in the rat hippocampus. Neuroscience. 1993 Dec;57(4):891–896. doi: 10.1016/0306-4522(93)90034-d. [DOI] [PubMed] [Google Scholar]
  21. Falkenberg T., Mohammed A. K., Henriksson B., Persson H., Winblad B., Lindefors N. Increased expression of brain-derived neurotrophic factor mRNA in rat hippocampus is associated with improved spatial memory and enriched environment. Neurosci Lett. 1992 Apr 13;138(1):153–156. doi: 10.1016/0304-3940(92)90494-r. [DOI] [PubMed] [Google Scholar]
  22. Funakoshi H., Frisén J., Barbany G., Timmusk T., Zachrisson O., Verge V. M., Persson H. Differential expression of mRNAs for neurotrophins and their receptors after axotomy of the sciatic nerve. J Cell Biol. 1993 Oct;123(2):455–465. doi: 10.1083/jcb.123.2.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ghosh A., Carnahan J., Greenberg M. E. Requirement for BDNF in activity-dependent survival of cortical neurons. Science. 1994 Mar 18;263(5153):1618–1623. doi: 10.1126/science.7907431. [DOI] [PubMed] [Google Scholar]
  24. Hengerer B., Lindholm D., Heumann R., Rüther U., Wagner E. F., Thoenen H. Lesion-induced increase in nerve growth factor mRNA is mediated by c-fos. Proc Natl Acad Sci U S A. 1990 May;87(10):3899–3903. doi: 10.1073/pnas.87.10.3899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Heumann R., Korsching S., Bandtlow C., Thoenen H. Changes of nerve growth factor synthesis in nonneuronal cells in response to sciatic nerve transection. J Cell Biol. 1987 Jun;104(6):1623–1631. doi: 10.1083/jcb.104.6.1623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hofer M. M., Barde Y. A. Brain-derived neurotrophic factor prevents neuronal death in vivo. Nature. 1988 Jan 21;331(6153):261–262. doi: 10.1038/331261a0. [DOI] [PubMed] [Google Scholar]
  27. Hofer M., Pagliusi S. R., Hohn A., Leibrock J., Barde Y. A. Regional distribution of brain-derived neurotrophic factor mRNA in the adult mouse brain. EMBO J. 1990 Aug;9(8):2459–2464. doi: 10.1002/j.1460-2075.1990.tb07423.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Humpel C., Wetmore C., Olson L. Regulation of brain-derived neurotrophic factor messenger RNA and protein at the cellular level in pentylenetetrazol-induced epileptic seizures. Neuroscience. 1993 Apr;53(4):909–918. doi: 10.1016/0306-4522(93)90476-v. [DOI] [PubMed] [Google Scholar]
  29. Hyman C., Hofer M., Barde Y. A., Juhasz M., Yancopoulos G. D., Squinto S. P., Lindsay R. M. BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature. 1991 Mar 21;350(6315):230–232. doi: 10.1038/350230a0. [DOI] [PubMed] [Google Scholar]
  30. Isackson P. J., Huntsman M. M., Murray K. D., Gall C. M. BDNF mRNA expression is increased in adult rat forebrain after limbic seizures: temporal patterns of induction distinct from NGF. Neuron. 1991 Jun;6(6):937–948. doi: 10.1016/0896-6273(91)90234-q. [DOI] [PubMed] [Google Scholar]
  31. Johnson J. E., Barde Y. A., Schwab M., Thoenen H. Brain-derived neurotrophic factor supports the survival of cultured rat retinal ganglion cells. J Neurosci. 1986 Oct;6(10):3031–3038. doi: 10.1523/JNEUROSCI.06-10-03031.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Jones K. R., Fariñas I., Backus C., Reichardt L. F. Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development. Cell. 1994 Mar 25;76(6):989–999. doi: 10.1016/0092-8674(94)90377-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Kaneda N., Sasaoka T., Kobayashi K., Kiuchi K., Nagatsu I., Kurosawa Y., Fujita K., Yokoyama M., Nomura T., Katsuki M. Tissue-specific and high-level expression of the human tyrosine hydroxylase gene in transgenic mice. Neuron. 1991 Apr;6(4):583–594. doi: 10.1016/0896-6273(91)90061-4. [DOI] [PubMed] [Google Scholar]
  34. Knüsel B., Beck K. D., Winslow J. W., Rosenthal A., Burton L. E., Widmer H. R., Nikolics K., Hefti F. Brain-derived neurotrophic factor administration protects basal forebrain cholinergic but not nigral dopaminergic neurons from degenerative changes after axotomy in the adult rat brain. J Neurosci. 1992 Nov;12(11):4391–4402. doi: 10.1523/JNEUROSCI.12-11-04391.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Knüsel B., Winslow J. W., Rosenthal A., Burton L. E., Seid D. P., Nikolics K., Hefti F. Promotion of central cholinergic and dopaminergic neuron differentiation by brain-derived neurotrophic factor but not neurotrophin 3. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):961–965. doi: 10.1073/pnas.88.3.961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kokaia Z., Gidö G., Ringstedt T., Bengzon J., Kokaia M., Siesjö B. K., Persson H., Lindvall O. Rapid increase of BDNF mRNA levels in cortical neurons following spreading depression: regulation by glutamatergic mechanisms independent of seizure activity. Brain Res Mol Brain Res. 1993 Sep;19(4):277–286. doi: 10.1016/0169-328x(93)90126-a. [DOI] [PubMed] [Google Scholar]
  37. Kokaia Z., Metsis M., Kokaia M., Bengzon J., Elmér E., Smith M. L., Timmusk T., Siesjö B. K., Persson H., Lindvall O. Brain insults in rats induce increased expression of the BDNF gene through differential use of multiple promoters. Eur J Neurosci. 1994 Apr 1;6(4):587–596. doi: 10.1111/j.1460-9568.1994.tb00303.x. [DOI] [PubMed] [Google Scholar]
  38. Koliatsos V. E., Clatterbuck R. E., Winslow J. W., Cayouette M. H., Price D. L. Evidence that brain-derived neurotrophic factor is a trophic factor for motor neurons in vivo. Neuron. 1993 Mar;10(3):359–367. doi: 10.1016/0896-6273(93)90326-m. [DOI] [PubMed] [Google Scholar]
  39. Korsching S. The neurotrophic factor concept: a reexamination. J Neurosci. 1993 Jul;13(7):2739–2748. doi: 10.1523/JNEUROSCI.13-07-02739.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Kraner S. D., Chong J. A., Tsay H. J., Mandel G. Silencing the type II sodium channel gene: a model for neural-specific gene regulation. Neuron. 1992 Jul;9(1):37–44. doi: 10.1016/0896-6273(92)90218-3. [DOI] [PubMed] [Google Scholar]
  41. Leibrock J., Lottspeich F., Hohn A., Hofer M., Hengerer B., Masiakowski P., Thoenen H., Barde Y. A. Molecular cloning and expression of brain-derived neurotrophic factor. Nature. 1989 Sep 14;341(6238):149–152. doi: 10.1038/341149a0. [DOI] [PubMed] [Google Scholar]
  42. Lindvall O., Ernfors P., Bengzon J., Kokaia Z., Smith M. L., Siesjö B. K., Persson H. Differential regulation of mRNAs for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the adult rat brain following cerebral ischemia and hypoglycemic coma. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):648–652. doi: 10.1073/pnas.89.2.648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Luckow B., Schütz G. CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987 Jul 10;15(13):5490–5490. doi: 10.1093/nar/15.13.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Metsis M., Timmusk T., Arenas E., Persson H. Differential usage of multiple brain-derived neurotrophic factor promoters in the rat brain following neuronal activation. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8802–8806. doi: 10.1073/pnas.90.19.8802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Morgan J. I., Curran T. Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenes fos and jun. Annu Rev Neurosci. 1991;14:421–451. doi: 10.1146/annurev.ne.14.030191.002225. [DOI] [PubMed] [Google Scholar]
  46. Mori N., Schoenherr C., Vandenbergh D. J., Anderson D. J. A common silencer element in the SCG10 and type II Na+ channel genes binds a factor present in nonneuronal cells but not in neuronal cells. Neuron. 1992 Jul;9(1):45–54. doi: 10.1016/0896-6273(92)90219-4. [DOI] [PubMed] [Google Scholar]
  47. Nilsson E., Lendahl U. Transient expression of a human beta-actin promoter/lacZ gene introduced into mouse embryos correlates with a low degree of methylation. Mol Reprod Dev. 1993 Feb;34(2):149–157. doi: 10.1002/mrd.1080340206. [DOI] [PubMed] [Google Scholar]
  48. Oppenheim R. W., Yin Q. W., Prevette D., Yan Q. Brain-derived neurotrophic factor rescues developing avian motoneurons from cell death. Nature. 1992 Dec 24;360(6406):755–757. doi: 10.1038/360755a0. [DOI] [PubMed] [Google Scholar]
  49. Palmiter R. D., Brinster R. L. Germ-line transformation of mice. Annu Rev Genet. 1986;20:465–499. doi: 10.1146/annurev.ge.20.120186.002341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Palmiter R. D., Sandgren E. P., Avarbock M. R., Allen D. D., Brinster R. L. Heterologous introns can enhance expression of transgenes in mice. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):478–482. doi: 10.1073/pnas.88.2.478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Patil N., Lacy E., Chao M. V. Specific neuronal expression of human NGF receptors in the basal forebrain and cerebellum of transgenic mice. Neuron. 1990 Mar;4(3):437–447. doi: 10.1016/0896-6273(90)90056-l. [DOI] [PubMed] [Google Scholar]
  52. Patterson S. L., Grover L. M., Schwartzkroin P. A., Bothwell M. Neurotrophin expression in rat hippocampal slices: a stimulus paradigm inducing LTP in CA1 evokes increases in BDNF and NT-3 mRNAs. Neuron. 1992 Dec;9(6):1081–1088. doi: 10.1016/0896-6273(92)90067-n. [DOI] [PubMed] [Google Scholar]
  53. Phillips H. S., Hains J. M., Laramee G. R., Rosenthal A., Winslow J. W. Widespread expression of BDNF but not NT3 by target areas of basal forebrain cholinergic neurons. Science. 1990 Oct 12;250(4978):290–294. doi: 10.1126/science.1688328. [DOI] [PubMed] [Google Scholar]
  54. Segal R. A., Takahashi H., McKay R. D. Changes in neurotrophin responsiveness during the development of cerebellar granule neurons. Neuron. 1992 Dec;9(6):1041–1052. doi: 10.1016/0896-6273(92)90064-k. [DOI] [PubMed] [Google Scholar]
  55. Sendtner M., Holtmann B., Kolbeck R., Thoenen H., Barde Y. A. Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section. Nature. 1992 Dec 24;360(6406):757–759. doi: 10.1038/360757a0. [DOI] [PubMed] [Google Scholar]
  56. Sieber-Blum M. Role of the neurotrophic factors BDNF and NGF in the commitment of pluripotent neural crest cells. Neuron. 1991 Jun;6(6):949–955. doi: 10.1016/0896-6273(91)90235-r. [DOI] [PubMed] [Google Scholar]
  57. Timmusk T., Belluardo N., Persson H., Metsis M. Developmental regulation of brain-derived neurotrophic factor messenger RNAs transcribed from different promoters in the rat brain. Neuroscience. 1994 May;60(2):287–291. doi: 10.1016/0306-4522(94)90242-9. [DOI] [PubMed] [Google Scholar]
  58. Timmusk T., Palm K., Metsis M., Reintam T., Paalme V., Saarma M., Persson H. Multiple promoters direct tissue-specific expression of the rat BDNF gene. Neuron. 1993 Mar;10(3):475–489. doi: 10.1016/0896-6273(93)90335-o. [DOI] [PubMed] [Google Scholar]
  59. Timmusk T., Persson H., Metsis M. Analysis of transcriptional initiation and translatability of brain-derived neurotrophic factor mRNAs in the rat brain. Neurosci Lett. 1994 Aug 15;177(1-2):27–31. doi: 10.1016/0304-3940(94)90036-1. [DOI] [PubMed] [Google Scholar]
  60. Vandaele S., Nordquist D. T., Feddersen R. M., Tretjakoff I., Peterson A. C., Orr H. T. Purkinje cell protein-2 regulatory regions and transgene expression in cerebellar compartments. Genes Dev. 1991 Jul;5(7):1136–1148. doi: 10.1101/gad.5.7.1136. [DOI] [PubMed] [Google Scholar]
  61. Vanselow J., Grabczyk E., Ping J., Baetscher M., Teng S., Fishman M. C. GAP-43 transgenic mice: dispersed genomic sequences confer a GAP-43-like expression pattern during development and regeneration. J Neurosci. 1994 Feb;14(2):499–510. doi: 10.1523/JNEUROSCI.14-02-00499.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Vidal M., Morris R., Grosveld F., Spanopoulou E. Tissue-specific control elements of the Thy-1 gene. EMBO J. 1990 Mar;9(3):833–840. doi: 10.1002/j.1460-2075.1990.tb08180.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Vornov J. J., Coyle J. T. Glutamate neurotoxicity and the inhibition of protein synthesis in the hippocampal slice. J Neurochem. 1991 Mar;56(3):996–1006. doi: 10.1111/j.1471-4159.1991.tb02020.x. [DOI] [PubMed] [Google Scholar]
  64. Wetmore C., Cao Y. H., Pettersson R. F., Olson L. Brain-derived neurotrophic factor: subcellular compartmentalization and interneuronal transfer as visualized with anti-peptide antibodies. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9843–9847. doi: 10.1073/pnas.88.21.9843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Wetmore C., Ernfors P., Persson H., Olson L. Localization of brain-derived neurotrophic factor mRNA to neurons in the brain by in situ hybridization. Exp Neurol. 1990 Aug;109(2):141–152. doi: 10.1016/0014-4886(90)90068-4. [DOI] [PubMed] [Google Scholar]
  66. Wetmore C., Olson L., Bean A. J. Regulation of brain-derived neurotrophic factor (BDNF) expression and release from hippocampal neurons is mediated by non-NMDA type glutamate receptors. J Neurosci. 1994 Mar;14(3 Pt 2):1688–1700. doi: 10.1523/JNEUROSCI.14-03-01688.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Wright E. M., Vogel K. S., Davies A. M. Neurotrophic factors promote the maturation of developing sensory neurons before they become dependent on these factors for survival. Neuron. 1992 Jul;9(1):139–150. doi: 10.1016/0896-6273(92)90229-7. [DOI] [PubMed] [Google Scholar]
  68. Yan Q., Elliott J., Snider W. D. Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death. Nature. 1992 Dec 24;360(6406):753–755. doi: 10.1038/360753a0. [DOI] [PubMed] [Google Scholar]
  69. Zafra F., Castrén E., Thoenen H., Lindholm D. Interplay between glutamate and gamma-aminobutyric acid transmitter systems in the physiological regulation of brain-derived neurotrophic factor and nerve growth factor synthesis in hippocampal neurons. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10037–10041. doi: 10.1073/pnas.88.22.10037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Zafra F., Hengerer B., Leibrock J., Thoenen H., Lindholm D. Activity dependent regulation of BDNF and NGF mRNAs in the rat hippocampus is mediated by non-NMDA glutamate receptors. EMBO J. 1990 Nov;9(11):3545–3550. doi: 10.1002/j.1460-2075.1990.tb07564.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Zimmerman L., Parr B., Lendahl U., Cunningham M., McKay R., Gavin B., Mann J., Vassileva G., McMahon A. Independent regulatory elements in the nestin gene direct transgene expression to neural stem cells or muscle precursors. Neuron. 1994 Jan;12(1):11–24. doi: 10.1016/0896-6273(94)90148-1. [DOI] [PubMed] [Google Scholar]
  72. da Penha Berzaghi M., Cooper J., Castrén E., Zafra F., Sofroniew M., Thoenen H., Lindholm D. Cholinergic regulation of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) but not neurotrophin-3 (NT-3) mRNA levels in the developing rat hippocampus. J Neurosci. 1993 Sep;13(9):3818–3826. doi: 10.1523/JNEUROSCI.13-09-03818.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES