Skip to main content
SpringerLink
Log in

Effects of experimental hypothyroidism on myelin sheath structural organization

  • Published:
Journal of Neurocytology

Abstract

A previous study using the 2′3′cyclic nucleotide 3′phosphodiesterase (CNPase), an oligodendroglial marker that also stain ensheathed fibers, showed a decrease in the number of immunoreactive fibers and a change in the pattern of CNPase immunoreactivity (CNPase+) in hypothyroid animals. CNPase+ fibers, in mature hypothyroid animals, showed a continuous pattern of staining in contrast with a discontinuous one in controls. As CNPase, in adult animals, can be found only in regions in which oligodendrocyte cytoplasm remains as internal, external and paranodal loops, it was suggested that the reduction of thyroid hormone levels leads to a failure in myelin compaction. Previous data showed a higher frequency of some abnormalities in myelin sheath as multiple cytoplasmic loops and redundant myelin profiles in mutant animals that present a failure in myelin compaction. The increase in the frequency of these abnormalities (multiple internal and external loops and redundant myelin) indicates a failure in the interrelations between the axons and the oligodendroglial processes. To verify if the thyroid hormone deficiency during CNS development disturbs these interrelations, we evaluated the frequency of the morphological abnormalities (multiple internal and external loops and redundant myelin) in myelin sheath of corpus callosum (cc) in experimental hypothyroidism. Randomic fields were kept by electron microscopy and the analysis of the frequency of morphological abnormalities showed a significant difference in hypothyroid animals at 60-day-old (PND60), with no significant differences at 90-day-old (PND90) animals. The frequency of multiple internal loops is higher in hypothyroid animals at PND60 that indicates a disturbance in the wrapping by the oligodendroglial process. These findings showed that thyroid hormone might modulate the axon-oligodendroglial relationships that are important for the adequate temporal sequence of events that occur during myelinogenesis, with possible consequences on myelin compaction.

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

  • ALMAZAN, G., HONEGGER, P. & MATTHIEU, J. M. (1985) Triiodothyronine stimulation of oligodendroglial differentiation and myelination. Developmental Neuroscience 7, 45-54.

    Google Scholar 

  • BARRADAS, P., GOMES, S. & CAVALCANTE, L. (1995) CNPase expression in the developing opossum brain stem and cerebellum. NeuroReport 6, 289-292.

    Google Scholar 

  • BARRADAS, P. C., FERRAZ, A. S., FERREIRA, A. A., DAUMAS, R. P. & MOURA, E. G. (2000) 2′3′ Cyclic nucleotide 3′ phosphodiesterase immunohistochemistry shows an impairment on myelin compaction in hypothyroid rats. International Journal of Developmental Neuroscience 18, 887-892.

    Google Scholar 

  • BARRADAS, P. C., VIEIRA, R. S. & DE FREITAS, M. S. (2001) Selective effect of hypothyroidism on expresion of myelin markers during development. Journal of Neuroscience Research 66, 254-261.

    Google Scholar 

  • BARRES, B. A., LAZAR, M. A. & RAFF, M. C. (1994) A novel role for thyroid hormone, glucocorticoids and retinoic acid in timing oligodendrocyte development. Development 120, 1097-1108.

    Google Scholar 

  • BERNAL, J. (2002) Action of thyroid hormone in brain. Journal of Endocrinological Investigation 25, 268-288.

    Google Scholar 

  • BERRY, M., HUNTER, A. S., DUNCAN, A., LORDAN, J., KIRVELL, S., TSANG, W.-L. & BUTT, A. M. (1998) Axon-glial relations during regeneration of axons in the adult rat anterior medullary vellum. Journal of Neurocytology 27, 915-937.

    Google Scholar 

  • BHAT, R. N., SARLIEVE, L. L., SBBA, R. G. & PIERINGER, R. A. (1979) Investigation on myelination “in vitro”. Regulation by thyroid hormone in cultures of dissociated brain cells from embryonic mice. Journal of Biological Chemistry 254, 9342-9344.

    Google Scholar 

  • BOSIO, A., BUSSOW, H., ADAM, J. & STOFFEL, W. (1998) Galactosphingolipids and axono-glial interaction in myelin of the central nervous system. Cell and Tissue Research 292, 199-210.

    Google Scholar 

  • BRAUN, P. E., SANDILLON, F., EDWARDS, A., MATTHIEU, J. M. & PRIVAT, A. (1988) Immunocytochemical localization by electron microscopy of 2′3′-cyclic nucleotide 3′-phosphodiesterase in developing oligodendrocytes of normal and mutant brain. Journal of Neuroscience 8, 3057-3066.

    Google Scholar 

  • BURY, F., CARRÉ, J-L., VEGA, S., GHANDOUR, M. S., RODRIGUEZ-PEÑA, A., LANGLEY, K. & SARLIÈVE, L. L. (2002) Coexpression of thyroid hormone receptor isoforms in mouse oligodendrocytes. Journal of Neuroscience Research 67, 106-113.

    Google Scholar 

  • CAMPAGNONI, A. T. & MACKLIN, W. B. (1988) Cellular and molecular aspects of myelin protein gene expression. Molecular Neurobiology 2, 41-89.

    Google Scholar 

  • COETZEE, T., SUZUKI, K., NAVE, K.-A. & POPKO, B. (1999) Myelination in the absence of galactolipids and proteolipid proteins. Molecular and Cellular Neuroscience 14, 41-51.

    Google Scholar 

  • DUPREE, J. L., COETZEE, T., SUZUKI, K. & POPKO, B. (1998a) Myelin abnormalities in mice deficient in galactocerebroside and sulfatide. Journal of Neurocytology 27, 649-659.

    Google Scholar 

  • DUPREE, J. L., SUZUKI, K. & POPKO, B. (1998b) Galactolipids in the formation and function of the myelin sheath. Microscopy Research and Technique 41, 431-440.

    Google Scholar 

  • FIERRO-RENOY, J. F., SZUCHE, S., FALCONE, M., MACCHIA, E. & DE GROOT, L. (1995) Three different thyroid hormone receptor isoforms are detected in a pure culture of ovine oligodendrocytes. Glia 14, 322-328.

    Google Scholar 

  • GRAVEL, C. & HAWKES, R. (1990) Maturation of the corpus callosum of the rat. I-Influence of thyroid hormones on the topography of callosal projections. Journal of Comparative Neurology 291, 128-146.

    Google Scholar 

  • GRAVEL, C., SASSEVILLE, R. & HAWKES, R. (1990) Maturation of the corpus callosum of the rat. II—Influence of thyroid hormones on the number and maturation of axons. Journal of Comparative Neurology 291, 147-161.

    Google Scholar 

  • GRIFFITHS, G., KLUGMANN, M., ANDERSON, T., YOOL, D., THOMSON, C., SCHWAB, M. H., SCHNEIDER, A., ZIMMERMANN, F., MCCULLOCH, M., NADON, N. & NAVE, K. A. (1998) Axonal swellings and degeneration in mice lacking the major proteolipid of myelin. Science 280, 1610-1613.

    Google Scholar 

  • HOLZ, A. & SCHWAB, M. E. (1997) Developmental expression of the myelin gene MOBP in the rat nervous system. Journal of Neurocytology 26, 467-477.

    Google Scholar 

  • IBARROLA, N. & RODRIGUEZ-PEÑA, A. (1997) Hypothyroidism coordinately and transiently affects myelin protein gene expression in most rat brain regions during postnatal development. Brain Research 752, 285-293.

    Google Scholar 

  • KANFER, J., PARENTY, M., GOUICT-ZALC, C., MUNGE, M., BERNIER, L., CAMPAGNONI, A. T., DAUTIGNY, A. & ZALC, B. (1989) Developmental expression of myelin proteolipid protein, myelin basic protein, and 2′3′-cyclic nucleotide 3′-phosphodiesterase transcripts in different brain regions. Journal of Molecular Neuroscience 1, 39-46.

    Google Scholar 

  • LAPPE-SIEFKE, C., GOEBBELS, S., GRAVEL, M., NICKSCH, E., LEE, J., BRAUN, P. E., GRIFFITHS, I. R. & NAVE, K.-A. (2003) Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination. Nature Genetics 33, 366-374.

    Google Scholar 

  • LIU, P.-S., WANG, Y.-J. & TSENG, G.-F. (2003) Close axonal injury of rubrospinal neurons induced transient perineuronal astrocytic and microglial reaction that coincided with their massive degeneration. Experimental Neurology 179, 111-126.

    Google Scholar 

  • MORELL, P., QUARLES, R. H. & NORTON, W. T. (1999) Myelin formation, structure, and biochemistry. In: Basic Neurochemistry: Molecular, Cellular and Medical Aspects (edited by UHLER, M. P.) pp. 69-94. New York: Lippincott-Raven.

    Google Scholar 

  • PORTERFIELD, S. P. & HENDRICH, C. E. (1993) The role of thyroid hormones in prenatal and neonatal neurological development—Current perspective. Endocrine Reviews 14, 94-106.

    Google Scholar 

  • RODRIGUEZ-PEÑA, A., IBARROLA, N., INIGUEZ, M. A., MUNOZ, A. & BERNAL, J. (1993) Neonatal hypothyroidism affects the timely expression of myelin-associated glycoprotein in the rat brain. Journal of Clinical Investigation 91, 812-818.

    Google Scholar 

  • ROGISTER, B., BEN-HUR, T. & DUBOIS-DALCQ, M. (1999) From neural stem cells to myelinating oligodendrocytes. Molecular and Cellular Neuroscience 14, 287-300.

    Google Scholar 

  • ROOTS, B. (1995). The evolution of myelinating cells. In Neuron-Glia Interrelations during Phylogeny: I. Phylogeny and Ontogeny of Glial Cells (edited by VERNADAKIS, A. & ROOTS, B.) pp. 223-248. Totowa: Humana Press.

    Google Scholar 

  • ROSENBLUTH, J. (1980) Peripheral myelin in the mouse mutant Shiverer. Journal of Comparative Neurology 193, 729-739.

    Google Scholar 

  • ROSMAN, N. P. & MALONE, M. J. (1977) Brain myelination in experimental hypothyroidism: Morphological and biochemical observations. In: Thyroid Hormones an Brain Development (edited by GRAVE, G. D.) pp. 169-198. New York: Raven Press.

    Google Scholar 

  • TOSIC, M., TORCH, S., COMTE, V., DOLIVO, M., HONNEGER, P. & MATTHIEU, J.-M. (1992) Triiodothyronine has diverse and multiple stimulating effects on expression of the major myelin protein genes. Journal of Neurochemistry 59, 1770-1777.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departamento Farmacologia e Psicobiologia, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Brazil

    Andréa A. Ferreira, José C. Nazário & Penha C. Barradas

  2. Departamento Ciências Fisiológicas, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Brazil

    Mário J. S. Pereira

  3. Departamento Histologia e Embriologia, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Brazil

    Neide L. Azevedo

Authors
  1. Andréa A. Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. José C. Nazário
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mário J. S. Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Neide L. Azevedo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Penha C. Barradas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Penha C. Barradas.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ferreira, A.A., Nazário, J.C., Pereira, M.J.S. et al. Effects of experimental hypothyroidism on myelin sheath structural organization. J Neurocytol 33, 225–231 (2004). https://doi.org/10.1023/B:NEUR.0000030697.78488.63

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:NEUR.0000030697.78488.63

Keywords

Search

Navigation