Europe PMC

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy.

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.

Free full text 


Logo of pnasLink to Publisher's site
Proc Natl Acad Sci U S A. 1991 Nov 15; 88(22): 10352–10356.
PMCID: PMC52926
PMID: 1946455

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

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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.9M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Kreutzberg GW. 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. [Europe PMC free article] [Abstract] [Google Scholar]
  • 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. [Abstract] [Google Scholar]
  • Barry J, Dubois MP, Poulain P. LRF producing cells of the mammalian hypothalamus. A fluorescent antibody study. Z Zellforsch Mikrosk Anat. 1973 Dec 31;146(3):351–366. [Abstract] [Google Scholar]
  • 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. [Europe PMC free article] [Abstract] [Google Scholar]
  • Hanson M, Edström A. Mitosis inhibitors and axonal transport. Int Rev Cytol Suppl. 1978;(7):373–402. [Abstract] [Google Scholar]
  • Ceccatelli S, Villar MJ, 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. [Europe PMC free article] [Abstract] [Google Scholar]
  • 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. [Abstract] [Google Scholar]
  • Cortés R, Villar MJ, 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. [Europe PMC free article] [Abstract] [Google Scholar]
  • Lieberman AR. The axon reaction: a review of the principal features of perikaryal responses to axon injury. Int Rev Neurobiol. 1971;14:49–124. [Abstract] [Google Scholar]
  • 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. [Abstract] [Google Scholar]
  • Pioro EP, Cuello AC. 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. [Abstract] [Google Scholar]
  • Levi-Montalcini R. The nerve growth factor 35 years later. Science. 1987 Sep 4;237(4819):1154–1162. [Abstract] [Google Scholar]
  • Barde YA, Edgar D, Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO J. 1982;1(5):549–553. [Europe PMC free article] [Abstract] [Google Scholar]
  • Leibrock J, Lottspeich F, Hohn A, Hofer M, Hengerer B, Masiakowski P, Thoenen H, Barde YA. Molecular cloning and expression of brain-derived neurotrophic factor. Nature. 1989 Sep 14;341(6238):149–152. [Abstract] [Google Scholar]
  • Hohn A, Leibrock J, Bailey K, Barde YA. 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. [Abstract] [Google Scholar]
  • Maisonpierre PC, Belluscio L, Squinto S, Ip NY, Furth ME, Lindsay RM, Yancopoulos GD. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science. 1990 Mar 23;247(4949 Pt 1):1446–1451. [Abstract] [Google Scholar]
  • Rosenthal A, Goeddel DV, Nguyen T, Lewis M, Shih A, Laramee GR, Nikolics K, Winslow JW. Primary structure and biological activity of a novel human neurotrophic factor. Neuron. 1990 May;4(5):767–773. [Abstract] [Google Scholar]
  • 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. [Abstract] [Google Scholar]
  • Ernfors P, Ibáez CF, 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. [Europe PMC free article] [Abstract] [Google Scholar]
  • Hallbök F, Ibáez CF, 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. [Abstract] [Google Scholar]
  • 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. [Abstract] [Google Scholar]
  • Hofer M, Pagliusi SR, Hohn A, Leibrock J, Barde YA. Regional distribution of brain-derived neurotrophic factor mRNA in the adult mouse brain. EMBO J. 1990 Aug;9(8):2459–2464. [Europe PMC free article] [Abstract] [Google Scholar]
  • 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. [Abstract] [Google Scholar]
  • Phillips HS, Hains JM, Laramee GR, Rosenthal A, Winslow JW. Widespread expression of BDNF but not NT3 by target areas of basal forebrain cholinergic neurons. Science. 1990 Oct 12;250(4978):290–294. [Abstract] [Google Scholar]
  • 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. [Abstract] [Google Scholar]
  • Lauterborn JC, Isackson PJ, Gall CM. 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. [Abstract] [Google Scholar]
  • 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. [Europe PMC free article] [Abstract] [Google Scholar]
  • Gall C, Murray K, Isackson PJ. 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. [Abstract] [Google Scholar]
  • 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. [Abstract] [Google Scholar]
  • Schalling M, Franco-Cereceda A, Hemsén A, Dagerlind A, Seroogy K, Persson H, Hökfelt T, Lundberg JM. 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. [Abstract] [Google Scholar]
  • Whittemore SR, 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. [Europe PMC free article] [Abstract] [Google Scholar]
  • Jones KR, Reichardt LF. 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. [Europe PMC free article] [Abstract] [Google Scholar]
  • Isackson PJ, Huntsman MM, Murray KD, Gall CM. 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. [Abstract] [Google Scholar]
  • Goldschmidt RB, 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. [Europe PMC free article] [Abstract] [Google Scholar]
  • Lu B, Yokoyama M, Dreyfus CF, Black IB. NGF gene expression in actively growing brain glia. J Neurosci. 1991 Feb;11(2):318–326. [Abstract] [Google Scholar]
  • Hyman C, Hofer M, Barde YA, Juhasz M, Yancopoulos GD, Squinto SP, Lindsay RM. BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature. 1991 Mar 21;350(6315):230–232. [Abstract] [Google Scholar]
  • Knüsel B, Winslow JW, Rosenthal A, Burton LE, Seid DP, 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. [Europe PMC free article] [Abstract] [Google Scholar]
  • Richardson PM, Issa VM, Riopelle RJ. Distribution of neuronal receptors for nerve growth factor in the rat. J Neurosci. 1986 Aug;6(8):2312–2321. [Abstract] [Google Scholar]
  • Schwab ME, 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. [Abstract] [Google Scholar]
  • Seiler M, Schwab ME. 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. [Abstract] [Google Scholar]
  • 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. [Abstract] [Google Scholar]
  • 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. [Europe PMC free article] [Abstract] [Google Scholar]
  • Shelton DL, Reichardt LF. 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. [Europe PMC free article] [Abstract] [Google Scholar]
  • Lu B, Buck CR, Dreyfus CF, Black IB. 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. [Abstract] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Citations & impact 


Impact metrics

Jump to Citations

Citations of article over time

Article citations


Go to all (75) article citations

Funding 


Funders who supported this work.

NIA NIH HHS (1)

NIMH NIH HHS (1)

NINDS NIH HHS (1)