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Regulation of semaphorin 3A expression in neurons of the rat spinal cord and cerebral cortex after transection injury

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Abstract

Semaphorin 3A (Sema3A) is a secreted repulsive axon guidance protein. It appears to play important roles in axon fasciculation, branching, neuronal migration, and tissue differentiation during embryonic development. In adults, Sema3A is expressed in spinal motoneurons and in some neurons in the brain. Here, we demonstrate changes in Sema3A expression in the spinal cord after complete transection and in the brain after spinal cord hemisection at the Th8 level in laboratory rats. Semi-quantitative reverse transcriptase-PCR analysis showed that the expression of Sema3A mRNA, which was present in the normal spinal cord, rapidly decreased after transection, reaching its lowest level 1 day after injury. Thereafter, Sema3A expression levels recovered and reached four-fifths of the normal level at 28 days. Double staining by in situ hybridization and fluorescence immunohistochemistry showed that Sema3A was expressed in NeuN-positive neurons, but not in glia in the spinal cord. Sema3A expression was up-regulated in the contralateral cerebral cortex and in the ipsilateral spinal trigeminal nucleus 1–3 days after spinal cord hemisection. It is likely that the up-regulation occurred in neurons whose descending fibers were transected. These results suggest that Sema3A is regulated differently in spinal motoneurons and brain neurons following axonal injury.

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References

  1. Chen MS, Huber AB, Haar ME van der, Frank M, Schnell L, Spillmann AA, Christ F, Schwab ME (2000) Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 403:434–439

    Article  CAS  PubMed  Google Scholar 

  2. De Winter F, Oudega M, Lankhorst AJ, Hamers FP, Blits B, Ruitenberg MJ, Pasterkamp RJ, Gispen WH, Verhaagen J (2002) Injury- induced class 3 semaphorin expression in the rat spinal cord. Exp Neurol 175:61–75

    Google Scholar 

  3. Fall WM (1984) Axonal endings terminating on dendrites of identified large trigeminal nucleus oralis. Brain Res 324:335–341

    Article  PubMed  Google Scholar 

  4. Fujita H, Zhang B, Sato K, Tanaka J, Sakanaka M (2001) Expressions of neuropilin-1, neuropilin-2 and demaphorin3A mRNA in the rat brain after middle cerebral artery occlusion. Brain Res 914:1–14

    Article  CAS  PubMed  Google Scholar 

  5. Gagliardini V, Fankhauser C (1999) Semaphorin III can induce death in sensory neurons. Mol Cell Neurosci 14:301–316

    Article  CAS  PubMed  Google Scholar 

  6. Giger RJ, Wolfer DP, De Wit GMJ, Verhaagen J (1996) Anatomy of rat semaphorin III/collapsin-1 mRNA expression and relationship to developing nerve tracts during neuroembryogenesis. J Comp Neurol 375:378–392

    Article  CAS  PubMed  Google Scholar 

  7. Giger RJ, Pasterkamp J, Heijnen S, Holtmaat AJGD, Verhaagen J (1998) Anatomical distribution of the chemorepellent semaphorin III/collapsin-1 in the adult rat and human brain: predominant expression in structures of the olfactory-hippocampal pathway and the motor system. J Neurosci Res 52:27–42

    Article  CAS  PubMed  Google Scholar 

  8. Hashimoto M, Koda M, Ino H, Murakami M, Yamazaki M, Hideshige M (2003) Up-regulation of osteopontin expression in rat spinal cord microglia after traumatic injury. J Neurotrauma 20:287–296

    Article  PubMed  Google Scholar 

  9. Ikeda O, Murakami M, Ino H, Yamazaki M, Nemoto T, Koda M, Nakayama C Hideshige M (2001) Acute up-regulation of brain-derived neurotrophic factor expression resulting from experimentally induced injury in the rat spinal cord. Acta Neuropathol 100:69–74

    Google Scholar 

  10. Ikeda O, Murakami M, Ino H, Yamazaki M, Koda M, Nakayama C Hideshige M (2002) Effects of brain-derived neurotrophic factor (BDNF) on compression-induced spinal cord injury: BDNF attenuates down-regulation of superoxide dismutase expression and promotes up-regulation of myelin basic protein expression. J Neuropathol Exp Neurol 61:142–153

    Google Scholar 

  11. Kawakami A, Kitsukawa T, Takagi S, Fujisawa H (1996) Developmentally regulated expression of a cell surface protein, neuropilin, in the mouse nervous system. J Neurobiol 29:1–17

    Article  CAS  PubMed  Google Scholar 

  12. Kolodkin AL, Matthes DJ, Goodman CS (1993) The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules. Cell 75:1389–1399

    CAS  PubMed  Google Scholar 

  13. Kolodkin AL, Levengood DV, Rowe EG, Tai Y-T, Giger RJ, Ginty DD (1997) Neuropilin is a semaphorin III receptor. Cell 90:753–762

    CAS  PubMed  Google Scholar 

  14. Laywell ED, Dorries U, Bartsch U, Faissner A, Schachner M, Steindler DA (1992) Enhanced expression of the developmentally regulated extracellular matrix molecule tenascin following adult brain injury. Proc Natl Acad Sci USA 89:2634–2638

    CAS  PubMed  Google Scholar 

  15. Leroy T, Brown JR (1971) Projection and termination of the corticospinal tract in rodents. Exp Brain Res 13:432–450

    PubMed  Google Scholar 

  16. Livesey FJ, Hunt SP (1997) Netrin and netrin receptor expression in the embryonic mammalian nervous system suggests roles in retinal, striatal, nigral, and cerebellar development. Mol Cell Neurosci 8:417–429

    Article  CAS  PubMed  Google Scholar 

  17. Luo Y, Raible D, Raper JA (1993) Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones. Cell 75:217–227

    CAS  PubMed  Google Scholar 

  18. McKeon RJ, Schreiber RC, Rudge JS, Silver J (1991) Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes. J Neurosci 11:3398–3411

    CAS  PubMed  Google Scholar 

  19. Messersmith EK, Leonardo ED, Shatz CJ, Tessier-Lavigne M, Goodman CS, Kolodkin AL (1995) Semaphorin III can function as a selective chemorepellent to pattern sensory projections in the spinal cord. Neuron 14:949–959

    CAS  PubMed  Google Scholar 

  20. Miranda JD, White LA, Marcillo AE, Willson CA, Jagid J, Whittemore SR (1999) Induction of Eph B3 after spinal cord injury. Exp Neurol 156:218–222

    Article  CAS  PubMed  Google Scholar 

  21. Pasterkamp RJ, Giger RJ, Verhaagen J (1998) Regulation of semaphorin III/collapsin-1 gene expression during peripheral nerve regeneration. Exp Neurol 153:313–327

    Article  CAS  PubMed  Google Scholar 

  22. Pasterkamp RJ, Giger RJ, Ruitenberg M-J, Holtmaat AJGD, De Wit J, De Winter F, Verhaagen J (1999) Expression of the gene encoding the chemorepellent Semaphorin III is induced in the fibroblast component of neural scar tissue formed following injuries of adult but not neonatal CNS. Mol Cell Neurosci 13:143–166

    CAS  PubMed  Google Scholar 

  23. Pasterkamp RJ, Anderson PN, Verhaagen J (2001) Peripheral nerve injury fails to induce growth of lesioned ascending dorsal column axons into spinal cord scar tissue expressing the axon repellent semaphorin3A. Eur J Neurosci 13:457–471

    Article  CAS  PubMed  Google Scholar 

  24. Reza JN, Gavazzi I, Cohen J (1999) Neuropilin-1 is expressed on adult mammalian dorsal root ganglion neurons and mediates semaphorin3a/collapsin-1-induced growth cone collapse by small diameter sensory afferents. Mol Cell Neurosci 14:317–326

    Article  CAS  PubMed  Google Scholar 

  25. Shirvan A, Ziv I, Fleminger G, Shina R, He Z, Brudo I, Melamed E, Barzilai A (1999) Semaphorins as mediators of neuronal apotosis. J Neurochem 73:961–971

    Google Scholar 

  26. Snow DM, Lemmon V, Carrino DA, Kaplan AI, Silver J (1990) Sulfated proteoglycans in astroglial barriers inhibit neurite outgrowth in vitro. Exp Neurol 109:111–130

    CAS  PubMed  Google Scholar 

  27. Stichel CC, Wunderlich G, Schwab ME, Muller HW (1995) Clearance of myelin constituents and axonal sprouting in the transected postcommissural fornix of the adult rat. Eur J Neurosci 7:401–411

    CAS  PubMed  Google Scholar 

  28. Stoll G, Griffin JW, Li CY, Trapp BD (1989) Wallerian degeneration in the peripheral nervous system: Participation of both Schwann cells and macrophages in myelin degradation. J Neurocytol 18:671–683

    CAS  PubMed  Google Scholar 

  29. Takahashi T, Fournier A, Nakamura F, Wang L-H, Murakami Y, Kalb RG, Fujisawa H, Strittmatter SM (1999) Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors. Cell 99:59–69

    CAS  PubMed  Google Scholar 

  30. Tanelian DL, Barry MA, Johnston SA, Le T, Smith GM (1997) Semaphorin III can repulse and inhibit adult sensory afferents in vivo. Nat Med 3:1398–1401

    CAS  PubMed  Google Scholar 

  31. Zhang Y, Winterbottom JK, Schachner M, Lieberman AR, Anderson PN (1997) Tenascin-C expression and axonal sprouting following injury to the spinal dorsal columns in the adult rat. J Neurosci Res 49:433–450

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by Grants-in-aid for Scientific Research to M. Murakami from the Ministry of Education, Science and Culture of Japan. We thank Dr. J. L. Verhaagen (Netherlands Institute for Brain Research, Amsterdam, The Netherlands) for kindly providing the plasmid containing Sema3A cDNA, and Drs. Osamu Ikeda and Arata Nakajima, Chiba University Graduate School of Medicine, for their technical advice and useful discussions.

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, 260-8677, Chiba, Japan

    Masayuki Hashimoto, Masao Koda, Masazumi Murakami, Katsunori Yoshinaga, Masashi Yamazaki & Hideshige Moriya

  2. Department of Neurobiology, Graduate School of Medicine, Chiba University, Chiba, Japan

    Hidetoshi Ino

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  1. Masayuki Hashimoto
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  2. Hidetoshi Ino
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  4. Masazumi Murakami
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  5. Katsunori Yoshinaga
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  6. Masashi Yamazaki
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  7. Hideshige Moriya
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Correspondence to Masayuki Hashimoto.

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Hashimoto, M., Ino, H., Koda, M. et al. Regulation of semaphorin 3A expression in neurons of the rat spinal cord and cerebral cortex after transection injury. Acta Neuropathol 107, 250–256 (2004). https://doi.org/10.1007/s00401-003-0805-z

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  • DOI: https://doi.org/10.1007/s00401-003-0805-z

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