Skip to main content
SpringerLink
Log in

Demyelination in the spinal cord of murine globoid cell leukodystrophy (the twitcher mouse)

  • Original Works
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

Chronologic events of demyelination were investigated in the spinal cord of the twicher mouse, an authentic murine model of human globoid cell leukodystrophy (GLD) from 5 to 45 days postnatal. There was very little evidence of myelin degeneration before day 25 although clustered or scattered globoid cells were already noted in the dorsal columns and intramedullary portion of the ventral roots.

Globoid cells contained typical cytoplasmic inclusions and in those which were found adjacent to degenerating myelin and naked axons, myelin debris were conspicuous in their cytoplasm.

Vesiculation of myelin and a feature of globoid cells stripping myelin lamellae were noted in the area of demyelination. Myelin and oligodendroglial degeneration became pronounced throughout the spinal white matter after day 40 but globoid cells tended to be more concentrated in the dorsal columns.

Our observations suggest that the emergence of globoid cells in GLD is in response to the changes in biochemical environment (i.e., excessive presence of galactosylceramide in the tissue?), and these cells appear to have a role as phagocytic cells in removing myelin lamellae.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Andrews JM, Cancilla PA (1970) Cytoplasmic inclusions in globoid cell leukodystrophy. Arch Pathol 89:53–55

    Google Scholar 

  • Andrews JM, Cancilla PA, Grippo J, Menkes JH (1971) Globoid cell leukodystrophy (Krabbe's disease). Morphological and biochemical studies. Neurology (Minneap) 21:337–352

    Google Scholar 

  • Andrews JM, Menkes JH (1970) Ultrastructure of experimentally produced globoid cells in the rat. Exp Neurol 29:483–493

    Google Scholar 

  • Anzil AP, Blinzinger K, Mehraein P, Dorn G, Neuhauser G (1972) Cytoplasmic inclusions in a child affected with Krabbe's disease (globoid cell leukodystrophy) and in the rabbit injected with galactocerebrosides. J Neuropathol Exp Neurol 31:370–388

    Google Scholar 

  • Austin JH (1963) Studies in globoid (Krabbe) leukodystrophy. I. The significance of lipid abnormalities in white matter in 8 globoid and 13 control patients. Arch Neurol 9:207–231

    Google Scholar 

  • Austin JH, Lehfeldt D (1965) Studies in globoid (Krabbe) leukodystrophy. III. Significance of experimentally produced globoid-like elements in rat white matter and spleen. J Neuropathol Exp Neurol 24:265–289

    Google Scholar 

  • Balentine JD (1978) Pathology of experimental spinal cord trauma. II. Ultrastructure of axons and myelin. Lab Invest 39:254–266

    Google Scholar 

  • D'Agostino AN, Sayre GP, Hayles AB (1963) Krabbe's disease: Globoid cell type of leukodystrophy. Arch Neurol 8:82–112

    Google Scholar 

  • Dal Canto MC, Lipton HL (1975) Primary demyelination in Theiler's virus infection: An ultrastructural study. Lab Invest 33:626–637

    Google Scholar 

  • Dal Canto MC, Wisniewski HM, Johnson AB, Brostoff SW, Raine CS (1975) Vesicular disruption of myelin in autoimmune demyelination. J Neurol Sci 24:313–319

    Google Scholar 

  • Dubois-Dalcq M, Niedieck B, Buyse M (1970) Action of anticerebroside sera on myelinated nervous tissue culture. Pathol Eur 5:331–347

    Google Scholar 

  • Duchen LW, Eicher EM, Jacobs JM, Scaravilli F, Texeira F (1980) Hereditary leukodystrophy in the mouse: The new mutant twicher. Brain 103:695–710

    Google Scholar 

  • Dunn HG, Dolman CL, Farrell DF, Tischler B, Hasinoff C, Wolf LS (1976) Krabbe's leukodystrophy without globoid cells. Neurology 26:1035–1041

    Google Scholar 

  • Eto Y, Suzuki K, Suzuki K (1970) Globoid cell leukodystrophy (Krabbe disease): Isolation of myelin with normal glycolipid composition. J Lipid Res 11:473–479

    Google Scholar 

  • Fletcher TF, Jessen CR, Bender AP (1977) Quantitative evaluation of spinal cord lesions in canine globoid leukodystrophy. J Neuropathol Exp Neurol 36:84–99

    Google Scholar 

  • Fletcher TF, Lee DG, Hammer RF (1971) Ultrastructural features of globoid cell leukodystrophy in the dog. Am J Vet Res 32:177–181

    Google Scholar 

  • Friede RL (1975) Developmental neuropathology. Springer, New York Wien, pp 433–442

    Google Scholar 

  • Fry JM, Weissbarth S, Lehrer GM, Bornstein MB (1974) Cerebroside antibody inhibit sulfatide synthesis and myelination and demyelination in cord tissue culture. Science 183:540–542

    Google Scholar 

  • Hall SM (1972) The effect of injections of lysophosphatidyl choline into white matter of the adult mouse spinal cord. J Cell Sci 10:535–546

    Google Scholar 

  • Igisu H, Takahashi H, Suzuki K, Suzuki K (1983) Abnormal accumulation of galactosylceramide in the kidney of twitcher mouse. Biochem Biophys Res Commun 110:940–944

    Google Scholar 

  • Ireland W, Fletcher T, Bingham C (1981) Quantification of microvasculature in the canine spinal cord. Anat Rec 200:103–113

    Google Scholar 

  • Jortner BS, Jonas AM (1968) The neuropathology of globoid-cell leucodystrophy in the dog. Acta Neuropathol (Berl) 10:171–182

    Google Scholar 

  • Kobayashi T, Nagara H, Suzuki K, Suzuki K (1982) The twitcher mouse: Determination of genetic status by galactosylceramidase assays on clipped tail. Biochem Med 27:8–14

    Google Scholar 

  • Lampert PW (1978) Autoimmune and virus-induced demyelinating disease. A review. Am J Pathol 91:175–208

    Google Scholar 

  • Lampert PW, Sims KJ, Kniazeff AJ (1973) Mechanism of demyelination in JHM virus encephalomyelitis. Acta Neuropathol (Berl) 24:76–85

    Google Scholar 

  • Martin JJ, Leroy JG, Ceuterick C, Libert J, Dodinval P, Martin L (1981) Fetal Krabbe leukodystrophy. A morphologic study of two cases. Acta Neuropathol (Berl) 53:87–91

    Google Scholar 

  • McKeever PE, Balentine JD (1978) Macrophage migration through the brain parenchyma to the perivascular space following particle injection. Am J Pathol 93:153–164

    Google Scholar 

  • Mei Liu H (1970) Ultrastructure of globoid leukodystrophy (Krabbe's disease) with reference to the origin of globoid cells. J Neuropathol Exp Neurol 29:441–462

    Google Scholar 

  • Nagara H, Kobayashi T, Suzuki K, Suzuki K (1982) The twitcher mouse: Normal pattern of early myelination in the spinal cord. Brain Res 244:289–294

    Google Scholar 

  • Nagara H, Suzuki K (1982) Radial component of the central myelin in neurologic mutant mice. Lab Invest 47:51–59

    Google Scholar 

  • Norton W (1977) Isolation and characterization of myelin. In: Morell P (ed) Myelin. Plenum Press, New York, pp 161–199

    Google Scholar 

  • Norton WT, Poduslo SE (1966) Metachromatic leukodystrophy: Chemically abnormal myelin and cerebral biopsy studies of three siblings. In: Ansell GB (ed) Variation in the chemical composition of the nervous system. Pergamon Press, Oxford, p 82

    Google Scholar 

  • Norton WT, Poduslo SE (1982) Biochemical studies of metachromatic leukodystrophy in three siblings. Acta Neuropathol (Berl) 57:188–196

    Google Scholar 

  • O'Brien JJ, Sampson EL (1966) Myelin membrane: A molecular abnormality. Science 150:1613–1614

    Google Scholar 

  • Okeda R, Suzuki Y, Horiguchi S, Fujii T (1979) Fetal globoid cell leukodystrophy in one of twins. Acta Neuropathol (Berl) 47: 151–154

    Google Scholar 

  • Olsson R, Scurander P, Svennerholm L (1966) Experimental studies on the pathogenesis of leukodystrophies. I. The effect of intracerebrally injected sphingolipid in the rat brain. Acta Neuropathol (Berl) 6:153–163

    Google Scholar 

  • Prineas J, Raine CS, Wisniewski H (1969) An ultrastructural study of experimental demyelination and remyelination. III. Chronic experimental allergic encephalomyelitis in the central nervous system. Lab Invest 21:472–483

    Google Scholar 

  • Saida T, Saida K, Brown MJ, Silberberg DH (1979) In vivo demyelination induced by intraneural injection of anti-galactocerebroside serum. A morphologic study. Am J Pathol 95:99–110

    Google Scholar 

  • Schlaepfer WW (1977) Vesicular disruption of myelin simulated by exposure of nerve to calcium ionophore. Nature 265:734–736

    Google Scholar 

  • Schochet SS Jr, Hardman JM, Lampert PW, Earle KM (1969) Krabbe's disease (globoid leukodystrophy). Electron microscopic observations. Arch Pathol 88:305–313

    Google Scholar 

  • Schochet SS Jr, McCormick WF, Powell GF (1976) Krabbe's disease: A light and electron microscopic study. Acta Neuropathol (Berl) 36:153–160

    Google Scholar 

  • Shaw CM, Carlson CB (1970) Crystalline structure in globoid epithelioid cells. J Neuropathol Exp Neurol 29:306–319

    Google Scholar 

  • Suzuki K (1970) Ultrastructural study of experimental globoid cells. Lab Invest 23:612–619

    Google Scholar 

  • Suzuki K, Grover WD (1970) Krabbe's leukodystrophy (globoid cell leukodystrophy). An ultrastructural study. Arch Neurol 22: 385–396

    Google Scholar 

  • Suzuki K, Suzuki Y (1983) Galactosylceramide lipidosis: Globoid cell leukodystrophy (Krabbe's disease). In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (eds) Metabolic basis of inherited disease. McGraw-Hill, New York, pp 857–880

    Google Scholar 

  • Takahashi H, Igisu H, Suzuki K, Suzuki K (1983a) The twitcher mouse: An ultrastructural study on the oligodendroglia. Acta Neuropathol (Berl) 59:159–166

    Google Scholar 

  • Takahashi H, Igisu H, Suzuki K, Suzuki K (1983b) Murine globoid cell leukodystrophy (the twitcher mouse): Presence of characteristic inclusions in kidney and lymphnode. Am J Pathol 112:147–154

    Google Scholar 

  • Takahashi H, Suzuki K (1982) Globoid cell leukodystrophy: Specialized contact of globoid cell with astrocyte in the brain of twitcher mouse. Acta Neuropathol (Berl) 58:237–242

    Google Scholar 

  • Yajima K (1980) Canine globoid cell leukodystrophy: Chronological neuropathological observations in the early lesion. Brain Dev 12:153–162

    Google Scholar 

  • Yajima K, Fletcher TF, Suzuki K (1977) Ultrastructural studies on canine globoid cell leukodystrophy. J Neurol Sci 33:179–197

    Google Scholar 

  • Yajima K, Suzuki K (1979) Demyelination and remyelination in the rat central nervous system following ethidium bromide injection. Lab Invest 41:385–392

    Google Scholar 

  • Yunis EJ, Lee RE (1969) The ultrastructure of globoid (Krabbe) leukodystrophy. Lab Invest 21:415–419

    Google Scholar 

  • Yunis EJ, Lee RE (1976) The morphological similarities of human and canine globoid cell leukodystrophy. Thin section and freezefracture studies. Am J Pathol 85:99–114

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology (Neuropathology), Albert Einstein College of Medicine, 10461, Bronx, NY, USA

    H. Takahashi & K. Suzuki

  2. Department of Neuroscience, Albert Einstein College of Medicine, 10461, Bronx, NY, USA

    H. Takahashi & K. Suzuki

  3. Rose F. Kennedy Center for Research in Mental Retardation and Human Development, Albert Einstein College of Medicine, 10461, Bronx, NY, USA

    H. Takahashi & K. Suzuki

Authors
  1. H. Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported in part by research grants NS-03356, NS-10803, and HD-01799 and a training grant for experimental neuropathology, NS-07098, from NINCDS

Rights and permissions

Reprints and permissions

About this article

Cite this article

Takahashi, H., Suzuki, K. Demyelination in the spinal cord of murine globoid cell leukodystrophy (the twitcher mouse). Acta Neuropathol 62, 298–308 (1984). https://doi.org/10.1007/BF00687612

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00687612

Key words

Search

Navigation