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Reorganization of nuclear compartments of type A neurons of trigeminal ganglia in response to inflammatory injury of peripheral nerve endings

  • Published:
Journal of Neurocytology

Abstract

In this study we have taken advantage of the high nuclear responsiveness of type A sensory ganglia neurons to variations of cellular activity to investigate the reorganization and dynamics of nuclear compartments involved in transcription and RNA processing in response to neuronal injury. As experimental model we have used the inflammatory injury of the peripheral nerve endings induced by formalin injection in the areas of ophthalmic/maxillary nerve distribution. We have performed immunofluorescence and confocal laser microscopy analysis with specific antibodies for different nuclear compartments and ultrastructural analysis. The initial response to neuronal injury, within the 3 days post-injury, consisted of chromatin condensation, reduction in the expression level of acetylated histone H4, accumulation of perichromatin granules, reorganization of splicing factors in prominent nuclear speckles, reduction in the number of Cajal bodies and nucleolar alterations. These changes tended to revert by day 7 post-injury and are consistent with a transient inhibition of transcription and RNA processing. Moreover, we have observed an early and sustained expression of the transcription factor c-Jun. These results illustrate the transcription-dependent organization of nuclear compartments in type A trigeminal neurons and also support the importance of the nuclear response to axonal injury as a key component in the regenerative capacity of this neuronal population.

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References

  • Berciano, M. T., Villagra, N. T., Pena, E., Navascues, J., Casafont, I. & Lafarga, M. (2002) Structural and functional compartmentalization of the cell nucleus in supraoptic neurons. Microscopy Re-search and Technique 56, 132–142.

    Google Scholar 

  • Berciano, M. T., Fernandez, R., Pena, E., Calle, E., Villagra, N. T. & Lafarga, M. (1999) Necro-sis of Schwann cells during tellurium-induced primary demyelination: DNA fragmentation, reorganization of splicing machinery, and formation of intranuclear rods of actin. Journal of Neuropathology and Experimental Neu-rology 58, 1234–1243.

    Google Scholar 

  • Bohmann, K., Ferreira, F. & Lamond, A. I. (1995) Mutational analysis of p80 coilin indicates a functional interaction between coiled bodies and the nucleolus. Journal of Cell Biology 131, 817–831.

    Google Scholar 

  • Brasch, K. (1990) Drug and metabolic-induced perturba-tions in nuclear structure and function: A review. Bio-chemistry and Cell Biology 68, 408–426.

    Google Scholar 

  • Brasch, K. & Ochs, R. L. (1992) Nuclear bodies: a newly “rediscovered” organelle. Experimental Cell Research 202, 211–223.

    Google Scholar 

  • Broude, E., Mcatee, M., Kelley, M. S. & Bregman, B. S. (1997) c-Jun expression in adult rat dorsal root gan-glion neurons: Differential response after central or pe-ripheral axotomy. Experimental Neurology 148, 367–377.

    Google Scholar 

  • Cajal, S. R. (1903) Un sencillo método de coloración se-lectiva del retículo protoplasmático y sus efectos en los diversosórganos nerviosos de vertebrados e invertebra-dos. Trabajos del Laboratorio de Investigaciones Biológicas 2, 129–221.

    Google Scholar 

  • Carmo-fonseca, M. (2002) The contribution of nu-clear compartmentalization to gene regulation. Cell 108, 513–521.

    Google Scholar 

  • Carmo-fonseca, M., Pepperkok, R., Carvalho, M. T. & Lamond, A.I. (1992) Transcription-dependent colocalization of the U1, U2, U4/U6, and U5 snRNPs in coiled bodies. Journal of Cell Biology 117,1–14.

    Google Scholar 

  • Carvalho, T., Almeida, F., Calapez, A., Lafarga, M. Berciano, M. T. & Carmo-fonseca, M. (1999) The spinal muscular atrophy disease gene product, SMN: A link between snRNP biogenesis and the Cajal (coiled) body. Journal of Cell Biology 147, 715–727.

    Google Scholar 

  • Cavanagh, J. B., Tomiwa, K. & Munro, P. M. G. (1987) Nuclear and nucleolar damage in adriamycin-induced toxicity to rat sensory ganglion cells. Neu-ropathology and Applied Neurobiology 13,23–38.

    Google Scholar 

  • Clark, P., Jones, K. I. & Lavelle, A. (1990) Ultra-stuctural and morphometric analysis of nucleolar and nuclear changes during the early growth period in hamster facial neurons. Journal of Comparative Neurology 302, 749–760.

    Google Scholar 

  • Cremer, T. &Cremer, C. (2001) Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nature Reviews Genetics 2, 292–301.

    Google Scholar 

  • De Felipe, J. & Hunt, S. P. (1994) The differential con-trol of c-jun expression in regeneration sensory neurons and their associated glial cells. Journal of Neuroscience 14, 2911–2923.

    Google Scholar 

  • De Leon, M., Nahin, R. L., Molina, C. A., De Leon, D. D. & Ruda, M. A. (1995) Comparison of cjun, junB, and junD mRNAexpression and protein in the rat dorsal root ganglia following sciatic nerve transaction. Journal of Neuroscience 42, 391–401.

    Google Scholar 

  • Dixon, A. D. (1963) Fine structure of nerve-cell bodies and satellite cells in the trigeminal ganglion. Journal of Dental Research 42, 990–999.

    Google Scholar 

  • Eisen M. B., Spellman, P. T., Brown P. O. & Botstein, D. (1998) Cluster analysis and display of genome-wide expression patterns. Proceedings of the National Academy of Sciences USA, 95, 14863–14868.

    Google Scholar 

  • Fakan, S. (1994) Perichromatin fibrils are in situ forms of nascent transcripts. Trends in Cell Biology 4,86–90.

    Google Scholar 

  • Gall J. G. (2000) Cajal bodies: The first 100 years. Annual Review of Cell and Developmental Biology 16, 273–300.

    Google Scholar 

  • Gillardon, F., Klimaschewski, L., Wickert, H., Krajewski, S., Reed, J. C. & Zimmermann, M. (1996) Expression pattern of candidate cell death effector proteins Bax, Bcl-2, Bcl-X, and c-Jun in sensory and motor neurons following sciatic nerve transection in the rat. Brain Research 739, 244–250.

    Google Scholar 

  • Gregory, P. D., Wagner, K. & Horz, W. (2001) His-tone Acetylation and chromatin remodelling. Experimen-tal Cell Research 265, 195–202.

    Google Scholar 

  • Habets, W. J., Hoet, M. H., Sillekens, P. T., De Rooij, D. J., Van de Putte, L. B. & Van Venrooij, W. J. (1989) Detection of autoantibodies in a quantitative immunoassay using recombinant ribonucle-oprotein antigens. Clinical and Experimental Immunology 76, 172–177.

    Google Scholar 

  • Herdegen, T., Skene, P. & BÄhr, M. (1997) The c-Jun protein – transcriptional mediator of neuronal survival, regeneration and death. Trends in Neuroscience 20, 227–231.

    Google Scholar 

  • jaskelioff, M. & Peterson, C. L. (2003) Chromatin and transcription: histones continue to make their marks. Nature Cell Biology 5, 395–399.

    Google Scholar 

  • Jenkins, R., Mcmahon S. B., Bond, A. B. & Hunt, S. P. (1993) Expression of c-Jun as a response to dorsal root and peripheral nerve section in damaged and adja-cent intact primary sensory neurons in the rat. European Journal of Neuroscience5, 751–759.

    Google Scholar 

  • Ji, R.R. & Rupp, F. (1997) Phosphorylation of transcription factor CREB in rat spinal cord after formalin-induced hy-peralgesia: relationship to c-fos induction. Journal of Neu-roscience 17, 1776–1785.

    Google Scholar 

  • Jolly, C. & Morimoto, M. I. (1999) Stress and the cell nucleus: Dynamics of gene expression and structural re-organization. Gene Expression 7, 216–270.

    Google Scholar 

  • Jordan, E. G. & Mcgovern, J. H. (1981) The quantita-tive relationship of the fibrillar centres on other nucleolar components to changes in growth conditions, serum de-privation and low doses of actinomycin D in cultured diploid fibroblasts (strain MRC-5). Journal of Cell Science 52, 373–389.

    Google Scholar 

  • Kenney, A. M. & Kocsis, J. D. (1997a) Temporal variabil-ity of jun family transcription factor levels in peripherally or centrally transected adult rat dorsal root ganglia. Brain Research Molecular Brain Research 52,53–61.

    Google Scholar 

  • Kenny, A. M. & Kocsis, J. D. (1997b) Timing of c-jun protein induction in lumbar dorsal root ganglia after.404 NAVASCUES, CASAFONT, VILLAGRA, LAFARGA andBERCIANO sciatic nerve transection varies with lesion distance. Brain Research 751,90–95.

    Google Scholar 

  • Kenney, A. M. &Kocsis, J. D. (1998) Peripheral axotomy induces long-term c-Jun amino-terminal kinase-1 activation and activator protein-1 binding activity by c-Jun and junD in adult rat dorsal root ganglia In vivo. Journal of Neuroscience 18, 1318–1328.

    Google Scholar 

  • Koberna, K., Malinsky J., Pliss A., Masata M., Vecerova J., Fialova, M., Bednar J. &Raska, I. (2002) Ribosomal genes in focus: new transcripts label the dense fibrillar components and form clusters indica-tive of “Christmas trees” in situ. Journal Cell Biology 157, 743–748.

    Google Scholar 

  • Lafarga, M., Berciano, M. T., Andres, M. A. & Testillano, P. S. (1994) Effects of cycloheximide on the structural organization of the nucleolus andthe coiled body in normal and stimulated supraoptic neurons of the rat. Journal of Neurocytology 23, 500–513.

    Google Scholar 

  • Lafarga, M., AndrÉs, M. A., Berciano, M. T. & Maquiera, E. (1991) Organization of nucleoli and nu-clear bodies in osmotically stimulated supraoptic neu-rons of the rat. Journal of Comparative Neurology 308, 329–339.

    Google Scholar 

  • Lafarga. M., Berciano, M. T., GarcÍa-Segura, M., AndrÊs, M. A. & Carmo-Fonseca, M. (1998) Acute osmotic/stress stimuli induce a transient decrease of transcriptional activity in the neurosecretory neurons of supraoptic nuclei. Journal of Neurocytology 27, 205–217.

    Google Scholar 

  • Lagares, A. & AvendaÑo, C. (2000) Lateral asymme-tries in the trigeminal ganglion of the male rat. Brain Re-search 865, 202–210.

    Google Scholar 

  • Lamond, A. I. & Earnshaw, W. C. (1998) Structure and function in the nucleus. Science 280, 547–553.

    Google Scholar 

  • Leong S. K., Liu H.P. & Yeo J. F. (2000) Nitric oxide synthase and glutamate receptor inmunoreactivity in the rat spinal trigeminal neurons expressing Fos protein after formalin injection. Brain Research 855, 107–115.

    Google Scholar 

  • Lieberman, A. R. (1976) Sensory ganglia. In The Peripheral Nerve (edited by LANDON, D. N.) pp. 188–278. London: Chapman and Hall.

    Google Scholar 

  • Malatesta, M., Bertoni-Freddari, C., Fattoretti, P., Caporaloni, C., Fakan, S. & Gazanelli, G. (2003) Altered RNA struc-tural constituents in aging and vitamin E deficiency. Mechanisms of Ageing and Development 124, 175–181.

    Google Scholar 

  • Matera, A. G. (1999) Nuclear bodies: Multifaceted subdo-mains of the interchromatin space. Trends in Cell Biology 9, 302–309.

    Google Scholar 

  • Mielke, K. & Herdegen, T. (2000) JNK and p38 stress kinases–Degenerative effectors of signal-transduction-cascades in the nervous system. Progress in Neurobiology 61,45–60.

    Google Scholar 

  • Misteli, T., Caceres, J. F. & Spector, D. L. (1997) The dynamics of a pre-m-RNA splicing factor in living cells. Nature 387, 523–527.

    Google Scholar 

  • Neubert, J. K., Maidment, N. T., Matsuka Y., Adelson D. W., Kruger, L. & Spigelman, I. (2000) Inflammation-induced changes in primary afferent-evoked release of substance P within trigeminal ganglia in vivo. Brain Research 871, 181-191.

    Google Scholar 

  • Olson, M. O. J., Hingorani, K. & Szebeni, A. (2002) Conventional and nonconventional roles of the nucleo-lus. International Review of Cytology 219, 199–266.

    Google Scholar 

  • Pederson, T. & Politz, J. C. (2000) The nucleolus and the four ribonucleoproteins of translation. Journal of Cell Biology 148, 1091–1096.

    Google Scholar 

  • Pena, E., Berciano, M. T., Fernandez, R., Crespo, P. &Lafarga, M. (2000) Stress-induced ac-tivation of c-Jun N-terminal kinase in sensory ganglion neurons: Accumulation in nuclear domains enriched in splicing factors and distribution in perichromatin fibrils. Experimental Cell Research 256, 179–191.

    Google Scholar 

  • Pena, E., Berciano, M. T., Fernandez, R., Ojeda, J. L. & Lafarga, M. (2001) Neuronal body size correlates with the number of nucleoli and Cajal bodies, and with the organization of the splicing machinery in rat trigeminal ganglion neurons. Journal of Comparative Neurology 430, 250–263.

    Google Scholar 

  • Plehn-Dujowich, D., Bell, P., Ishow, A. M., Baumann, C. & Maul, G. G. (2000) Non-apoptotic chromosome condensation induced by stress: delineation of interchromosomal spaces. Chromosoma 109, 266–279.

    Google Scholar 

  • Proudfoot, N. (2000) Connecting transcription to mes-senger RNA processing. Trends in Biochemical Sciences 25, 290–293.

    Google Scholar 

  • Puvion-Dutilleul, F. & Puvion, E. (1981) Relation-ship between chromatin and perichromatin granules in cadmium-treated isolated hepatocytes. Journal of Ultra-structure Research 7, 341–350.

    Google Scholar 

  • Rambourg, A., Clermont, Y. & Beaudet, A. (1983) Ultrastructural features of six types of neurons in rat dor-sal root ganglia. Journal of Neurocytology 12,47–66.

    Google Scholar 

  • Roth, S. Y., Denu, J. M. & Allis, C. D. (2001) Histone acetyltransferases. Annual Reviews of Biochemistry 70,81–120.

    Google Scholar 

  • Scheer, U. & Benavente, R. (1990) Functional and dy-namic aspects of the mammalian nucleolus. Bio Essays 12, 14–21.

    Google Scholar 

  • Shaw, P. J. &Jordan, E. G. (1995) The nucleolus. Annual Review of Cell and Developmental Biology 11,93–121.

    Google Scholar 

  • Spector, D. L. (2001) Nuclear domains. Journal of Cell Sci-ence 114, 2891–2893.

    Google Scholar 

  • Storer, P. D. & Jones, K. J. (2003) Ribosomal RNA transcriptional activation and processing in hamster rubrospinal motoneurons: Effects of axotomy and testosterone treatment. Journal of Comparative Neurology 458, 326–333.

    Google Scholar 

  • Stoyanova, B. B. & Hadjiolov, A. A. (1979) Alterations in the processing of rat-liver ribosomal RNA caused by cycloheximide inhibition of protein synthesis. European Journal of Biochemistry 96, 349–356.

    Google Scholar 

  • Sugiura, Y., Kitoh, J. & Sakai, H. (1983) A comparative ultrastructural study of the trigeminal ganglion in the rat and chicken. Journal of Morphology 175, 101–113.

    Google Scholar 

  • Tandrup, T. & Jakobsen, J. (2002) Long-term acry-lamide intoxication induces atrophy of dorsal root gan-glion A-cells and of myelinated sensory axons. Journal of Neurocytology 23, 79–87.

    Google Scholar 

  • Tomiwa, K., Nolan, C. & Cavanagh, J. B. (1986) The effects of cisplatin on rat spinal ganglia: a study by light and electron microscopy and by morphometry. Acta Neuropathologica 69, 295–308.

    Google Scholar 

  • Vio-cigna, M., Pebusque, M. J. & SeÏte, R. (1982) Im-provements in selective silver staining of nucleolar orga-nizer regions in block tissues at the ultrastructural level. Biology of the Cell 44, 329–332.

    Google Scholar 

  • Williams, R. R. E. (2003) Transcription and the territory: The ins and outs of gene positioning. Trends in Genetics 19, 298–302.

    Google Scholar 

  • Woolf, C. J. & Costigan, M. (1999) Transcriptional and posttranslational plasticity and the generation of inflam matory pain. Proceedings of the National Academy of Sciences of U.S.A. 96, 7723–7730.

    Google Scholar 

  • Zeng, C., Kim, E., Warren, S.L. & Berget, S. M. (1997) Dynamic relocation of transcription and splicing factors dependent upon transcriptional activity. EMBO Journal 16, 1401–1412.

    Google Scholar 

  • Zimmermann, M. (1983) Ethical guidelines for investiga-tion of experimental pain in conscious animals. Pain 16, 109–110.

    Google Scholar 

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology and Biomedicine Unit Associated with C.S.I.C., University of Cantabria, Santander, Spain

    J. Navascues, I. Casafont, N. T. Villagra, M. Lafarga & M. T. Berciano

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  1. J. Navascues
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  2. I. Casafont
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  3. N. T. Villagra
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  4. M. Lafarga
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Navascues, J., Casafont, I., Villagra, N.T. et al. Reorganization of nuclear compartments of type A neurons of trigeminal ganglia in response to inflammatory injury of peripheral nerve endings. J Neurocytol 33, 393–405 (2004). https://doi.org/10.1023/B:NEUR.0000046570.90442.43

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