Accelerated Axonal Loss Following Acute CNS Demyelination in Mice Lacking Protein Tyrosine Phosphatase Receptor Type Z

Accelerated Axonal Loss Following Acute CNS Demyelination in Mice Lacking Protein Tyrosine Phosphatase Receptor Type Z

Author Huang, Jeffrey K. Google Scholar
Ferrari, Carina C. Google Scholar
Castro, Glaucia Monteiro de Autor UNIFESP Google Scholar
Lafont, David Google Scholar
Zhao, Chao Google Scholar
Zaratin, Paola Google Scholar
Pouly, Sandrine Google Scholar
Greco, Beatrice Google Scholar
Franklin, Robin J. M. Google Scholar
Institution Univ Cambridge
Universidade Federal de São Paulo (UNIFESP)
Merck Serono Int
Abstract Protein tyrosine phosphatase receptor type Z (Ptprz) is widely expressed in the mammalian central nervous system and has been suggested to regulate oligodendrocyte survival and differentiation. We investigated the role of Ptprz in oligodendrocyte remyelination after acute, toxin-induced demyelination in Ptprz null mice. We found neither obvious impairment in the recruitment of oligodendrocyte precursor cells, astrocytes, or reactive microglia/macrophage to lesions nor a failure for oligodendrocyte precursor cells to differentiate and remyelinate axons at the lesions. However, we observed an unexpected increase in the number of dystrophic axons by 3 days after demyelination, followed by prominent Wallerian degeneration by 21 days in the Ptprz-deficient mice. Moreover, quantitative gait analysis revealed a deficit of locomotor behavior in the mutant mice, suggesting increased vulnerability to axonal injury. We propose that Ptprz is necessary to maintain central nervous system axonal integrity in a demyelinating environment and may be an important target of axonal protection in inflammatory demyelinating diseases, such as multiple sclerosis and periventricular leukomalacia. (Am J Pathol 2012, 181:1518-1523; http://dx.doi.org/10.1016/j.ajpath.2012.07.011)
Language English
Sponsor UK Multiple Sclerosis Society
Multiple Sclerosis International Federation
Date 2012-11-01
Published in American Journal of Pathology. New York: Elsevier B.V., v. 181, n. 5, p. 1518-1523, 2012.
ISSN 0002-9440 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1518-1523
Origin http://dx.doi.org/10.1016/j.ajpath.2012.07.011
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000310656800005
URI http://repositorio.unifesp.br/handle/11600/35417

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