Abstract
Schwann cells are excluded from the CNS during development by the glial limiting membrane, an area of astrocytic specialisation present at the nerve root transitional zone, and at blood vessels in the neuropil. This barrier, however, can be disrupted and, with the highly migratory nature of Schwann cells, can result in their invasion and myelination of the CNS in many pathological situations. In this paper we demonstrate that this occurs in a number of myelin mutants, including the myelin deficient (md) and taiep rats and the canine shaking (sh) pup. While it is still relatively uncommon in the rodent mutants, the sh pup shows extensive Schwann cell invasion along the neuraxis. This invasion involves the spinal cord, brain stem, and cerebellum and increases in amount and distribution with age. In situ hybridisation studies using a P0 riboprobe suggest that the likely origin of these cells in the sh pup is the nerve roots, primarily the dorsal roots. Paradoxically, Schwann cell myelination of the CNS increases with time in the sh pup despite a marked, progressive gliosis involving the glia limitans and neuropil. Thus the mechanism by which these cells migrate into the CNS through the gliosed nerve root transitional zone or from vasa nervorum remains unknown. Extensive Schwann cell CNS myelination may have therapeutic significance in human myelin disease.
Keywords: Myelination, nerve root transitional zone, Schwann cell, mutants
Full Text
The Full Text of this article is available as a PDF (1.7 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adelman L. S., Aronson S. M. Intramedullary nerve fiber and Schwann cell proliferation within the spinal cord (schwannosis). Neurology. 1972 Jul;22(7):726–731. doi: 10.1212/wnl.22.7.726. [DOI] [PubMed] [Google Scholar]
- Baron-Van Evercooren A., Avellana-Adalid V., Ben Younes-Chennoufi A., Gansmuller A., Nait-Oumesmar B., Vignais L. Cell-cell interactions during the migration of myelin-forming cells transplanted in the demyelinated spinal cord. Glia. 1996 Feb;16(2):147–164. doi: 10.1002/(SICI)1098-1136(199602)16:2<147::AID-GLIA7>3.0.CO;2-0. [DOI] [PubMed] [Google Scholar]
- Baron-Van Evercooren A., Duhamel-Clerin E., Boutry J. M., Hauw J. J., Gumpel M. Pathways of migration of transplanted Schwann cells in the demyelinated mouse spinal cord. J Neurosci Res. 1993 Jul 1;35(4):428–438. doi: 10.1002/jnr.490350410. [DOI] [PubMed] [Google Scholar]
- Baron-Van Evercooren A., Gansmuller A., Duhamel E., Pascal F., Gumpel M. Repair of a myelin lesion by Schwann cells transplanted in the adult mouse spinal cord. J Neuroimmunol. 1992 Oct;40(2-3):235–242. doi: 10.1016/0165-5728(92)90139-c. [DOI] [PubMed] [Google Scholar]
- Berry M., Hall S., Follows R., Wyse J. P. Defective myelination in the optic nerve of the Browman-Wyse (BW) mutant rat. J Neurocytol. 1989 Apr;18(2):141–159. doi: 10.1007/BF01206658. [DOI] [PubMed] [Google Scholar]
- Berthold C. H., Carlstedt T. Observations on the morphology at the transition between the peripheral and the central nervous system in the cat. II. General organization of the transitional region in S1 dorsal rootlets. Acta Physiol Scand Suppl. 1977;446:23–42. [PubMed] [Google Scholar]
- Blakemore W. F., Crang A. J. The use of cultured autologous Schwann cells to remyelinate areas of persistent demyelination in the central nervous system. J Neurol Sci. 1985 Sep;70(2):207–223. doi: 10.1016/0022-510x(85)90088-7. [DOI] [PubMed] [Google Scholar]
- Blakemore W. F. Limited remyelination of CNS axons by Schwann cells transplanted into the sub-arachnoid space. J Neurol Sci. 1984 Jun;64(3):265–276. doi: 10.1016/0022-510x(84)90175-8. [DOI] [PubMed] [Google Scholar]
- Blakemore W. F., Patterson R. C. Observations on the interactions of Schwann cells and astrocytes following X-irradiation of neonatal rat spinal cord. J Neurocytol. 1975 Oct;4(5):573–585. doi: 10.1007/BF01351538. [DOI] [PubMed] [Google Scholar]
- Blakemore W. F., Patterson R. C. Observations on the interactions of Schwann cells and astrocytes following X-irradiation of neonatal rat spinal cord. J Neurocytol. 1975 Oct;4(5):573–585. doi: 10.1007/BF01351538. [DOI] [PubMed] [Google Scholar]
- Blakemore W. F. Remyelination of CNS axons by Schwann cells transplanted from the sciatic nerve. Nature. 1977 Mar 3;266(5597):68–69. doi: 10.1038/266068a0. [DOI] [PubMed] [Google Scholar]
- Blight A. R., Young W. Central axons in injured cat spinal cord recover electrophysiological function following remyelination by Schwann cells. J Neurol Sci. 1989 Jun;91(1-2):15–34. doi: 10.1016/0022-510x(89)90073-7. [DOI] [PubMed] [Google Scholar]
- Carlstedt T. Observations on the morphology at the transition between the peripheral and the central nervous system in the cat. I. A preparative procedure useful for electron microscopy of the lumbosacral dorsal. Acta Physiol Scand Suppl. 1977;446:5–22. [PubMed] [Google Scholar]
- Carlstedt T. Reinnervation of the mammalian spinal cord after neonatal dorsal root crush. J Neurocytol. 1988 Jun;17(3):335–350. doi: 10.1007/BF01187856. [DOI] [PubMed] [Google Scholar]
- Dal Canto M. C., Lipton H. L. Schwann cell remyelination and recurrent demyelination in the central nervous system of mice infected with attenuated Theiler's virus. Am J Pathol. 1980 Jan;98(1):101–122. [PMC free article] [PubMed] [Google Scholar]
- Duncan I. D., Aguayo A. J., Bunge R. P., Wood P. M. Transplantation of rat Schwann cells grown in tissue culture into the mouse spinal cord. J Neurol Sci. 1981 Feb;49(2):241–252. doi: 10.1016/0022-510x(81)90082-4. [DOI] [PubMed] [Google Scholar]
- Duncan I. D., Hammang J. P., Jackson K. F., Wood P. M., Bunge R. P., Langford L. Transplantation of oligodendrocytes and Schwann cells into the spinal cord of the myelin-deficient rat. J Neurocytol. 1988 Jun;17(3):351–360. doi: 10.1007/BF01187857. [DOI] [PubMed] [Google Scholar]
- Duncan I. D., Lunn K. F., Holmgren B., Urba-Holmgren R., Brignolo-Holmes L. The taiep rat: a myelin mutant with an associated oligodendrocyte microtubular defect. J Neurocytol. 1992 Dec;21(12):870–884. doi: 10.1007/BF01191684. [DOI] [PubMed] [Google Scholar]
- Duncan I. D., Nadon N. L., Hoffman R. L., Lunn K. F., Csiza C., Wells M. R. Oligodendrocyte survival and function in the long-lived strain of the myelin deficient rat. J Neurocytol. 1995 Oct;24(10):745–762. doi: 10.1007/BF01191211. [DOI] [PubMed] [Google Scholar]
- Fanarraga M. L., Griffiths I. R., McCulloch M. C., Barrie J. A., Kennedy P. G., Brophy P. J. Rumpshaker: an X-linked mutation causing hypomyelination: developmental differences in myelination and glial cells between the optic nerve and spinal cord. Glia. 1992;5(3):161–170. doi: 10.1002/glia.440050302. [DOI] [PubMed] [Google Scholar]
- Felts P. A., Smith K. J. Conduction properties of central nerve fibers remyelinated by Schwann cells. Brain Res. 1992 Mar 6;574(1-2):178–192. doi: 10.1016/0006-8993(92)90815-q. [DOI] [PubMed] [Google Scholar]
- Fraher J. P. The CNS-PNS transitional zone of the rat. Morphometric studies at cranial and spinal levels. Prog Neurobiol. 1992;38(3):261–316. doi: 10.1016/0301-0082(92)90022-7. [DOI] [PubMed] [Google Scholar]
- Franklin R. J., Blakemore W. F. Requirements for Schwann cell migration within CNS environments: a viewpoint. Int J Dev Neurosci. 1993 Oct;11(5):641–649. doi: 10.1016/0736-5748(93)90052-F. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Franklin R. J., Crang A. J., Blakemore W. F. Type 1 astrocytes fail to inhibit Schwann cell remyelination of CNS axons in the absence of cells of the O-2A lineage. Dev Neurosci. 1992;14(2):85–92. doi: 10.1159/000111651. [DOI] [PubMed] [Google Scholar]
- Gilmore S. A., Sims T. J., Heard J. K. Autoradiographic and ultrastructural studies of areas of spinal cord occupied by Schwann cells and Schwann cell myelin. Brain Res. 1982 May 13;239(2):365–375. doi: 10.1016/0006-8993(82)90515-7. [DOI] [PubMed] [Google Scholar]
- Griffin J. W., Drucker N., Gold B. G., Rosenfeld J., Benzaquen M., Charnas L. R., Fahnestock K. E., Stocks E. A. Schwann cell proliferation and migration during paranodal demyelination. J Neurosci. 1987 Mar;7(3):682–699. doi: 10.1523/JNEUROSCI.07-03-00682.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Griffiths I. R., McCulloch M. C. Nerve fibres in spinal cord impact injuries. Part 1. Changes in the myelin sheath during the initial 5 weeks. J Neurol Sci. 1983 Mar;58(3):335–349. doi: 10.1016/0022-510x(83)90093-x. [DOI] [PubMed] [Google Scholar]
- Griffiths I. R., Mitchell L. S., McPhilemy K., Morrison S., Kyriakides E., Barrie J. A. Expression of myelin protein genes in Schwann cells. J Neurocytol. 1989 Jun;18(3):345–352. doi: 10.1007/BF01190837. [DOI] [PubMed] [Google Scholar]
- Hall S. M. The Schwann cell: a reappraisal of its role in the peripheral nervous system. Neuropathol Appl Neurobiol. 1978 May-Jun;4(3):165–176. doi: 10.1111/j.1365-2990.1978.tb00533.x. [DOI] [PubMed] [Google Scholar]
- Hammang J. P., Worth S. F., Duncan I. D., Gilmore S. A. Proliferation of rat intraspinal Schwann cells following tellurium intoxication. Acta Neuropathol. 1988;76(6):624–627. doi: 10.1007/BF00689602. [DOI] [PubMed] [Google Scholar]
- Harrison B. M. Remyelination by cells introduced into a stable demyelinating lesion in the central nervous system. J Neurol Sci. 1980 Apr;46(1):63–81. doi: 10.1016/0022-510x(80)90044-1. [DOI] [PubMed] [Google Scholar]
- Harrison B. M. Schwann cells divide in a demyelinating lesion of the central nervous system. Brain Res. 1987 Apr 14;409(1):163–168. doi: 10.1016/0006-8993(87)90754-2. [DOI] [PubMed] [Google Scholar]
- Heard J. K., Gilmore S. A. Intramedullary Schwann cell development following x-irradiation of mid-thoracic and lumbosacral spinal cord levels in immature rats. Anat Rec. 1980 May;197(1):85–93. doi: 10.1002/ar.1091970108. [DOI] [PubMed] [Google Scholar]
- Honmou O., Felts P. A., Waxman S. G., Kocsis J. D. Restoration of normal conduction properties in demyelinated spinal cord axons in the adult rat by transplantation of exogenous Schwann cells. J Neurosci. 1996 May 15;16(10):3199–3208. doi: 10.1523/JNEUROSCI.16-10-03199.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inoue Y., Inoue K., Terashima T., Mikoshiba K., Tsukada Y. Developmental changes of oligodendroglia in the posterior funiculus of "Shiverer" mutant mouse spinal cord, with special reference to myelin formation. Anat Embryol (Berl) 1983;168(2):159–171. doi: 10.1007/BF00315814. [DOI] [PubMed] [Google Scholar]
- Itoyama Y., Ohnishi A., Tateishi J., Kuroiwa Y., Webster H. D. Spinal cord multiple sclerosis lesions in Japanese patients: Schwann cell remyelination occurs in areas that lack glial fibrillary acidic protein (GFAP). Acta Neuropathol. 1985;65(3-4):217–223. doi: 10.1007/BF00687001. [DOI] [PubMed] [Google Scholar]
- Itoyama Y., Webster H. D., Richardson E. P., Jr, Trapp B. D. Schwann cell remyelination of demyelinated axons in spinal cord multiple sclerosis lesions. Ann Neurol. 1983 Sep;14(3):339–346. doi: 10.1002/ana.410140313. [DOI] [PubMed] [Google Scholar]
- Lemke G., Axel R. Isolation and sequence of a cDNA encoding the major structural protein of peripheral myelin. Cell. 1985 Mar;40(3):501–508. doi: 10.1016/0092-8674(85)90198-9. [DOI] [PubMed] [Google Scholar]
- Lunn K. F., Fanarraga M. L., Duncan I. D. Myelin mutants: new models and new observations. Microsc Res Tech. 1995 Oct 15;32(3):183–203. doi: 10.1002/jemt.1070320303. [DOI] [PubMed] [Google Scholar]
- Miller D. J., Rivera-Quiñones C., Njenga M. K., Leibowitz J., Rodriguez M. Spontaneous CNS remyelination in beta 2 microglobulin-deficient mice following virus-induced demyelination. J Neurosci. 1995 Dec;15(12):8345–8352. doi: 10.1523/JNEUROSCI.15-12-08345.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moll C., Meier C. The central-peripheral transition zone of cervical spinal nerve roots in Jimpy mutant and normal mice. Light- and electron-microscopic study. Acta Neuropathol. 1983;60(3-4):241–251. doi: 10.1007/BF00691872. [DOI] [PubMed] [Google Scholar]
- Nadon N. L., Duncan I. D., Hudson L. D. A point mutation in the proteolipid protein gene of the 'shaking pup' interrupts oligodendrocyte development. Development. 1990 Oct;110(2):529–537. doi: 10.1242/dev.110.2.529. [DOI] [PubMed] [Google Scholar]
- Nagara H., Suzuki K. Chronological study of oligodendroglial alterations and myelination in quaking mice. Neuropathol Appl Neurobiol. 1981 Mar-Apr;7(2):135–149. doi: 10.1111/j.1365-2990.1981.tb00083.x. [DOI] [PubMed] [Google Scholar]
- Paíno C. L., Fernandez-Valle C., Bates M. L., Bunge M. B. Regrowth of axons in lesioned adult rat spinal cord: promotion by implants of cultured Schwann cells. J Neurocytol. 1994 Jul;23(7):433–452. doi: 10.1007/BF01207115. [DOI] [PubMed] [Google Scholar]
- Pender M. P. Recovery from acute experimental allergic encephalomyelitis in the Lewis rat. Early restoration of nerve conduction and repair by Schwann cells and oligodendrocytes. Brain. 1989 Apr;112(Pt 2):393–416. doi: 10.1093/brain/112.2.393. [DOI] [PubMed] [Google Scholar]
- Prineas J. W., Connell F. Remyelination in multiple sclerosis. Ann Neurol. 1979 Jan;5(1):22–31. doi: 10.1002/ana.410050105. [DOI] [PubMed] [Google Scholar]
- Raine C. S. On the occurrence of Schwann cells within the normal central nervous system. J Neurocytol. 1976 Jun;5(3):371–380. doi: 10.1007/BF01175122. [DOI] [PubMed] [Google Scholar]
- Raine C. S., Traugott U., Stone S. H. Glial bridges and Schwann cell migration during chronic demyelination in the C.N.S. J Neurocytol. 1978 Oct;7(5):541–553. doi: 10.1007/BF01260888. [DOI] [PubMed] [Google Scholar]
- Raisman G., Lawrence J. M., Brook G. A. Schwann cells transplanted into the CNS. Int J Dev Neurosci. 1993 Oct;11(5):651–669. doi: 10.1016/0736-5748(93)90053-g. [DOI] [PubMed] [Google Scholar]
- Rossiter J. P., Fraher J. P. Intermingling of central and peripheral nervous tissues in rat dorsolateral vagal rootlet transitional zones. J Neurocytol. 1990 Jun;19(3):385–407. doi: 10.1007/BF01188406. [DOI] [PubMed] [Google Scholar]
- Sims T. J., Gilmore S. A., Waxman S. G., Klinge E. Dorsal-ventral differences in the glia limitans of the spinal cord: an ultrastructural study in developing normal and irradiated rats. J Neuropathol Exp Neurol. 1985 Jul;44(4):415–429. doi: 10.1097/00005072-198507000-00005. [DOI] [PubMed] [Google Scholar]
- Wisniewski H. M., Madrid R. E. Chronic progressive experimental allergic encephalomyelitis (EAE) in adult guinea pigs. J Neuropathol Exp Neurol. 1983 May;42(3):243–255. doi: 10.1097/00005072-198305000-00003. [DOI] [PubMed] [Google Scholar]
- Yamamoto T., Kawamura J., Hashimoto S., Nakamura M. Extensive proliferation of peripheral type myelin in necrotic spinal cord lesions of multiple sclerosis. J Neurol Sci. 1991 Apr;102(2):163–169. doi: 10.1016/0022-510x(91)90064-e. [DOI] [PubMed] [Google Scholar]
