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. 1991 Nov 15;88(22):10352–10356. doi: 10.1073/pnas.88.22.10352

Expanded distribution of mRNA for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the rat brain after colchicine treatment.

S Ceccatelli 1, P Ernfors 1, M J Villar 1, H Persson 1, T Hökfelt 1
PMCID: PMC52926  PMID: 1946455

Abstract

The effect of intracerebroventricular injection of the mitosis inhibitor colchicine on expression of mRNA for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 was studied in the rat brain with in situ hybridization. Colchicine up-regulates mRNA for NGF and BDNF in many of the neuronal systems normally expressing these factors. In addition, after colchicine treatment NGF and BDNF mRNAs were localized in several brain areas where they normally cannot be detected. Thus, NGF mRNA was present, for example, in many motor nuclei and in the basal forebrain, and BDNF mRNA was seen in many nuclei in the brain stem and in catecholamine neurons, including dopamine neurons in the substantia nigra. The latter neurons have recently been shown to be sensitive to BDNF, and the present results show that these neurons can produce this factor themselves. A decrease in mRNA for BDNF and neurotrophin 3 was seen only in the granular-cell layer of the hippocampal formation. A strong hybridization signal for BDNF and neurotrophin 3 mRNA was also observed over several myelinated tracts in treated rats, supporting the hypothesis that glial cells as well as neurons can produce these trophic factors.

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Selected References

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

  1. Ayer-LeLievre C., Olson L., Ebendal T., Seiger A., Persson H. Expression of the beta-nerve growth factor gene in hippocampal neurons. Science. 1988 Jun 3;240(4857):1339–1341. doi: 10.1126/science.2897715. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Barry J., Dubois M. P., Poulain P. LRF producing cells of the mammalian hypothalamus. A fluorescent antibody study. Z Zellforsch Mikrosk Anat. 1973 Dec 31;146(3):351–366. doi: 10.1007/BF02346227. [DOI] [PubMed] [Google Scholar]
  4. Ceccatelli S., Villar M. J., Goldstein M., Hökfelt T. Expression of c-Fos immunoreactivity in transmitter-characterized neurons after stress. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9569–9573. doi: 10.1073/pnas.86.23.9569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cortés R., Ceccatelli S., Schalling M., Hökfelt T. Differential effects of intracerebroventricular colchicine administration on the expression of mRNAs for neuropeptides and neurotransmitter enzymes, with special emphasis on galanin: an in situ hybridization study. Synapse. 1990;6(4):369–391. doi: 10.1002/syn.890060410. [DOI] [PubMed] [Google Scholar]
  6. Cortés R., Villar M. J., Verhofstad A., Hökfelt T. Effects of central nervous system lesions on the expression of galanin: a comparative in situ hybridization and immunohistochemical study. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7742–7746. doi: 10.1073/pnas.87.19.7742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Ernfors P., Henschen A., Olson L., Persson H. Expression of nerve growth factor receptor mRNA is developmentally regulated and increased after axotomy in rat spinal cord motoneurons. Neuron. 1989 Jun;2(6):1605–1613. doi: 10.1016/0896-6273(89)90049-4. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Gall C., Murray K., Isackson P. J. Kainic acid-induced seizures stimulate increased expression of nerve growth factor mRNA in rat hippocampus. Brain Res Mol Brain Res. 1991 Jan;9(1-2):113–123. doi: 10.1016/0169-328x(91)90136-l. [DOI] [PubMed] [Google Scholar]
  12. Goldschmidt R. B., Steward O. Preferential neurotoxicity of colchicine for granule cells of the dentate gyrus of the adult rat. Proc Natl Acad Sci U S A. 1980 May;77(5):3047–3051. doi: 10.1073/pnas.77.5.3047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hallbök F., Ibáez C. F., Persson H. Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary. Neuron. 1991 May;6(5):845–858. doi: 10.1016/0896-6273(91)90180-8. [DOI] [PubMed] [Google Scholar]
  14. Hanson M., Edström A. Mitosis inhibitors and axonal transport. Int Rev Cytol Suppl. 1978;(7):373–402. [PubMed] [Google Scholar]
  15. 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]
  16. Hohn A., Leibrock J., Bailey K., Barde Y. A. Identification and characterization of a novel member of the nerve growth factor/brain-derived neurotrophic factor family. Nature. 1990 Mar 22;344(6264):339–341. doi: 10.1038/344339a0. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Hökfelt T., Dahlström A. Effects of two mitosis inhibitors (colchicine and vinblastine) on the distribution and axonal transport of noradrenaline storage particles, studied by fluorescence and electron microscopy. Z Zellforsch Mikrosk Anat. 1971;119(4):460–482. doi: 10.1007/BF00455243. [DOI] [PubMed] [Google Scholar]
  19. Hökfelt T., Ljungdahl A., Terenius L., Elde R., Nilsson G. Immunohistochemical analysis of peptide pathways possibly related to pain and analgesia: enkephalin and substance P. Proc Natl Acad Sci U S A. 1977 Jul;74(7):3081–3085. doi: 10.1073/pnas.74.7.3081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Jones K. R., Reichardt L. F. Molecular cloning of a human gene that is a member of the nerve growth factor family. Proc Natl Acad Sci U S A. 1990 Oct;87(20):8060–8064. doi: 10.1073/pnas.87.20.8060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kaisho Y., Yoshimura K., Nakahama K. Cloning and expression of a cDNA encoding a novel human neurotrophic factor. FEBS Lett. 1990 Jun 18;266(1-2):187–191. doi: 10.1016/0014-5793(90)81536-w. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Korsching S., Auburger G., Heumann R., Scott J., Thoenen H. Levels of nerve growth factor and its mRNA in the central nervous system of the rat correlate with cholinergic innervation. EMBO J. 1985 Jun;4(6):1389–1393. doi: 10.1002/j.1460-2075.1985.tb03791.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kreutzberg G. W. Neuronal dynamics and axonal flow. IV. Blockage of intra-axonal enzyme transport by colchicine. Proc Natl Acad Sci U S A. 1969 Mar;62(3):722–728. doi: 10.1073/pnas.62.3.722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lauterborn J. C., Isackson P. J., Gall C. M. Nerve growth factor mRNA-containing cells are distributed within regions of cholinergic neurons in the rat basal forebrain. J Comp Neurol. 1991 Apr 15;306(3):439–446. doi: 10.1002/cne.903060308. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Levi-Montalcini R. The nerve growth factor 35 years later. Science. 1987 Sep 4;237(4819):1154–1162. doi: 10.1126/science.3306916. [DOI] [PubMed] [Google Scholar]
  29. Lieberman A. R. The axon reaction: a review of the principal features of perikaryal responses to axon injury. Int Rev Neurobiol. 1971;14:49–124. doi: 10.1016/s0074-7742(08)60183-x. [DOI] [PubMed] [Google Scholar]
  30. Lu B., Buck C. R., Dreyfus C. F., Black I. B. Expression of NGF and NGF receptor mRNAs in the developing brain: evidence for local delivery and action of NGF. Exp Neurol. 1989 Jun;104(3):191–199. doi: 10.1016/0014-4886(89)90029-0. [DOI] [PubMed] [Google Scholar]
  31. Lu B., Yokoyama M., Dreyfus C. F., Black I. B. NGF gene expression in actively growing brain glia. J Neurosci. 1991 Feb;11(2):318–326. doi: 10.1523/JNEUROSCI.11-02-00318.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Maisonpierre P. C., Belluscio L., Squinto S., Ip N. Y., Furth M. E., Lindsay R. M., Yancopoulos G. D. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science. 1990 Mar 23;247(4949 Pt 1):1446–1451. doi: 10.1126/science.247.4949.1446. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Pioro E. P., Cuello A. C. Distribution of nerve growth factor receptor-like immunoreactivity in the adult rat central nervous system. Effect of colchicine and correlation with the cholinergic system--I. Forebrain. Neuroscience. 1990;34(1):57–87. doi: 10.1016/0306-4522(90)90304-m. [DOI] [PubMed] [Google Scholar]
  35. Richardson P. M., Issa V. M., Riopelle R. J. Distribution of neuronal receptors for nerve growth factor in the rat. J Neurosci. 1986 Aug;6(8):2312–2321. doi: 10.1523/JNEUROSCI.06-08-02312.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rosenthal A., Goeddel D. V., Nguyen T., Lewis M., Shih A., Laramee G. R., Nikolics K., Winslow J. W. Primary structure and biological activity of a novel human neurotrophic factor. Neuron. 1990 May;4(5):767–773. doi: 10.1016/0896-6273(90)90203-r. [DOI] [PubMed] [Google Scholar]
  37. Schalling M., Franco-Cereceda A., Hemsén A., Dagerlind A., Seroogy K., Persson H., Hökfelt T., Lundberg J. M. Neuropeptide Y and catecholamine synthesizing enzymes and their mRNAs in rat sympathetic neurons and adrenal glands: studies on expression, synthesis and axonal transport after pharmacological and experimental manipulations using hybridization techniques and radioimmunoassay. Neuroscience. 1991;41(2-3):753–766. doi: 10.1016/0306-4522(91)90365-u. [DOI] [PubMed] [Google Scholar]
  38. Schwab M. E., Otten U., Agid Y., Thoenen H. Nerve growth factor (NGF) in the rat CNS: absence of specific retrograde axonal transport and tyrosine hydroxylase induction in locus coeruleus and substantia nigra. Brain Res. 1979 Jun 8;168(3):473–483. doi: 10.1016/0006-8993(79)90303-2. [DOI] [PubMed] [Google Scholar]
  39. Seiler M., Schwab M. E. Specific retrograde transport of nerve growth factor (NGF) from neocortex to nucleus basalis in the rat. Brain Res. 1984 May 21;300(1):33–39. doi: 10.1016/0006-8993(84)91338-6. [DOI] [PubMed] [Google Scholar]
  40. Shelton D. L., Reichardt L. F. Studies on the expression of the beta nerve growth factor (NGF) gene in the central nervous system: level and regional distribution of NGF mRNA suggest that NGF functions as a trophic factor for several distinct populations of neurons. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2714–2718. doi: 10.1073/pnas.83.8.2714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Thoenen H., Bandtlow C., Heumann R. The physiological function of nerve growth factor in the central nervous system: comparison with the periphery. Rev Physiol Biochem Pharmacol. 1987;109:145–178. doi: 10.1007/BFb0031026. [DOI] [PubMed] [Google Scholar]
  42. 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]
  43. Whittemore S. R., Ebendal T., Lärkfors L., Olson L., Seiger A., Strömberg I., Persson H. Development and regional expression of beta nerve growth factor messenger RNA and protein in the rat central nervous system. Proc Natl Acad Sci U S A. 1986 Feb;83(3):817–821. doi: 10.1073/pnas.83.3.817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. 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]

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