Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Oct 15;89(20):9444–9448. doi: 10.1073/pnas.89.20.9444

Light regulates expression of brain-derived neurotrophic factor mRNA in rat visual cortex.

E Castrén 1, F Zafra 1, H Thoenen 1, D Lindholm 1
PMCID: PMC50148  PMID: 1409655

Abstract

Specific sensory input has profound transient and long-lasting effects on the function of corresponding sensory cortical areas both during development and in adulthood. To study whether neurotrophic factors might play a role in such processes, we investigated the effects of light on the nerve growth factor and brain-derived neurotrophic factor (BDNF) mRNA levels in rat visual cortex. Keeping adult rats in the dark or preventing normal activity of retinal ganglion cells by intraocular injection of tetrodotoxin significantly decreased the levels of BDNF mRNA in the visual cortex but not in other cortical areas. Exposure to light after a period in darkness rapidly restored the mRNA to control levels. These alterations in visual input had no effect on nerve growth factor mRNA. The mRNA of trkB, the putative signal-transducing receptor unit for BDNF, was also decreased in darkness, although less than BDNF mRNA. BDNF mRNA levels increased in the visual cortex of newborn rats after eye-opening. This increase is retarded, although not completely abolished, by rearing the pups in darkness. Thus, the levels of BDNF mRNA are rapidly regulated by sensory input during development and in adulthood. BDNF may therefore play an important role in formation and in activity-dependent modulation of specific connections in the visual cortex.

Full text

PDF
9444

Images in this article

9445Image
on p.9445
9445Image
on p.9445

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. 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]
  3. Bandtlow C. E., Meyer M., Lindholm D., Spranger M., Heumann R., Thoenen H. Regional and cellular codistribution of interleukin 1 beta and nerve growth factor mRNA in the adult rat brain: possible relationship to the regulation of nerve growth factor synthesis. J Cell Biol. 1990 Oct;111(4):1701–1711. doi: 10.1083/jcb.111.4.1701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  5. Constantine-Paton M., Cline H. T., Debski E. Patterned activity, synaptic convergence, and the NMDA receptor in developing visual pathways. Annu Rev Neurosci. 1990;13:129–154. doi: 10.1146/annurev.ne.13.030190.001021. [DOI] [PubMed] [Google Scholar]
  6. Domenici L., Berardi N., Carmignoto G., Vantini G., Maffei L. Nerve growth factor prevents the amblyopic effects of monocular deprivation. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8811–8815. doi: 10.1073/pnas.88.19.8811. [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., 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]
  9. Gall C. M., Isackson P. J. Limbic seizures increase neuronal production of messenger RNA for nerve growth factor. Science. 1989 Aug 18;245(4919):758–761. doi: 10.1126/science.2549634. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Gilbert C. D., Wiesel T. N. Receptive field dynamics in adult primary visual cortex. Nature. 1992 Mar 12;356(6365):150–152. doi: 10.1038/356150a0. [DOI] [PubMed] [Google Scholar]
  12. Hendry S. H., Jones E. G. Reduction in number of immunostained GABAergic neurones in deprived-eye dominance columns of monkey area 17. Nature. 1986 Apr 24;320(6064):750–753. doi: 10.1038/320750a0. [DOI] [PubMed] [Google Scholar]
  13. Hendry S. H., Kennedy M. B. Immunoreactivity for a calmodulin-dependent protein kinase is selectively increased in macaque striate cortex after monocular deprivation. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1536–1540. doi: 10.1073/pnas.83.5.1536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Hubel D. H., Wiesel T. N. The period of susceptibility to the physiological effects of unilateral eye closure in kittens. J Physiol. 1970 Feb;206(2):419–436. doi: 10.1113/jphysiol.1970.sp009022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Kaas J. H., Krubitzer L. A., Chino Y. M., Langston A. L., Polley E. H., Blair N. Reorganization of retinotopic cortical maps in adult mammals after lesions of the retina. Science. 1990 Apr 13;248(4952):229–231. doi: 10.1126/science.2326637. [DOI] [PubMed] [Google Scholar]
  18. Kaplan D. R., Martin-Zanca D., Parada L. F. Tyrosine phosphorylation and tyrosine kinase activity of the trk proto-oncogene product induced by NGF. Nature. 1991 Mar 14;350(6314):158–160. doi: 10.1038/350158a0. [DOI] [PubMed] [Google Scholar]
  19. Klein R., Conway D., Parada L. F., Barbacid M. The trkB tyrosine protein kinase gene codes for a second neurogenic receptor that lacks the catalytic kinase domain. Cell. 1990 May 18;61(4):647–656. doi: 10.1016/0092-8674(90)90476-u. [DOI] [PubMed] [Google Scholar]
  20. Klein R., Jing S. Q., Nanduri V., O'Rourke E., Barbacid M. The trk proto-oncogene encodes a receptor for nerve growth factor. Cell. 1991 Apr 5;65(1):189–197. doi: 10.1016/0092-8674(91)90419-y. [DOI] [PubMed] [Google Scholar]
  21. Klein R., Martin-Zanca D., Barbacid M., Parada L. F. Expression of the tyrosine kinase receptor gene trkB is confined to the murine embryonic and adult nervous system. Development. 1990 Aug;109(4):845–850. doi: 10.1242/dev.109.4.845. [DOI] [PubMed] [Google Scholar]
  22. Klein R., Nanduri V., Jing S. A., Lamballe F., Tapley P., Bryant S., Cordon-Cardo C., Jones K. R., Reichardt L. F., Barbacid M. The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3. Cell. 1991 Jul 26;66(2):395–403. doi: 10.1016/0092-8674(91)90628-c. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kleinschmidt A., Bear M. F., Singer W. Blockade of "NMDA" receptors disrupts experience-dependent plasticity of kitten striate cortex. Science. 1987 Oct 16;238(4825):355–358. doi: 10.1126/science.2443978. [DOI] [PubMed] [Google Scholar]
  24. Lindholm D., Heumann R., Hengerer B., Thoenen H. Interleukin 1 increases stability and transcription of mRNA encoding nerve growth factor in cultured rat fibroblasts. J Biol Chem. 1988 Nov 5;263(31):16348–16351. [PubMed] [Google Scholar]
  25. Lindholm Dan, Castrén Eero, Hengerer Bastian, Zafra Francisco, Berninger Benedikt, Thoenen Hans. Differential Regulation of Nerve Growth Factor (NGF) Synthesis in Neurons and Astrocytes by Glucocorticoid Hormones. Eur J Neurosci. 1992;4(5):404–410. doi: 10.1111/j.1460-9568.1992.tb00889.x. [DOI] [PubMed] [Google Scholar]
  26. Lu B., Yokoyama M., Dreyfus C. F., Black I. B. Depolarizing stimuli regulate nerve growth factor gene expression in cultured hippocampal neurons. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6289–6292. doi: 10.1073/pnas.88.14.6289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Middlemas D. S., Lindberg R. A., Hunter T. trkB, a neural receptor protein-tyrosine kinase: evidence for a full-length and two truncated receptors. Mol Cell Biol. 1991 Jan;11(1):143–153. doi: 10.1128/mcb.11.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Rodriguez-Tébar A., Dechant G., Barde Y. A. Binding of brain-derived neurotrophic factor to the nerve growth factor receptor. Neuron. 1990 Apr;4(4):487–492. doi: 10.1016/0896-6273(90)90107-q. [DOI] [PubMed] [Google Scholar]
  30. Schnürch H., Risau W. Differentiating and mature neurons express the acidic fibroblast growth factor gene during chick neural development. Development. 1991 Apr;111(4):1143–1154. doi: 10.1242/dev.111.4.1143. [DOI] [PubMed] [Google Scholar]
  31. Soppet D., Escandon E., Maragos J., Middlemas D. S., Reid S. W., Blair J., Burton L. E., Stanton B. R., Kaplan D. R., Hunter T. The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor. Cell. 1991 May 31;65(5):895–903. doi: 10.1016/0092-8674(91)90396-g. [DOI] [PubMed] [Google Scholar]
  32. Squinto S. P., Stitt T. N., Aldrich T. H., Davis S., Bianco S. M., Radziejewski C., Glass D. J., Masiakowski P., Furth M. E., Valenzuela D. M. trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor. Cell. 1991 May 31;65(5):885–893. doi: 10.1016/0092-8674(91)90395-F. [DOI] [PubMed] [Google Scholar]
  33. Vazquez M. E., Ebendal T. Messenger RNAs for trk and the low-affinity NGF receptor in rat basal forebrain. Neuroreport. 1991 Oct;2(10):593–596. doi: 10.1097/00001756-199110000-00010. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Whittemore S. R., Friedman P. L., Larhammar D., Persson H., Gonzalez-Carvajal M., Holets V. R. Rat beta-nerve growth factor sequence and site of synthesis in the adult hippocampus. J Neurosci Res. 1988 Aug;20(4):403–410. doi: 10.1002/jnr.490200402. [DOI] [PubMed] [Google Scholar]
  36. Wiesel T. N., Hubel D. H. Comparison of the effects of unilateral and bilateral eye closure on cortical unit responses in kittens. J Neurophysiol. 1965 Nov;28(6):1029–1040. doi: 10.1152/jn.1965.28.6.1029. [DOI] [PubMed] [Google Scholar]
  37. Wong-Riley M., Carroll E. W. Effect of impulse blockage on cytochrome oxidase activity in monkey visual system. Nature. 1984 Jan 19;307(5948):262–264. doi: 10.1038/307262a0. [DOI] [PubMed] [Google Scholar]
  38. Worley P. F., Christy B. A., Nakabeppu Y., Bhat R. V., Cole A. J., Baraban J. M. Constitutive expression of zif268 in neocortex is regulated by synaptic activity. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5106–5110. doi: 10.1073/pnas.88.12.5106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. 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]
  41. Zilles K., Wree A., Schleicher A., Divac I. The monocular and binocular subfields of the rat's primary visual cortex: a quantitative morphological approach. J Comp Neurol. 1984 Jul 1;226(3):391–402. doi: 10.1002/cne.902260308. [DOI] [PubMed] [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

RESOURCES