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

FERRARI , CC; HUANG, J; MONTEIRO DE CASTRO, G; LAFONT, D; CHAO, Z; ZARATIN, P; GRECO, B; FRANKLIN, JM

AMERICAN JOURNAL OF PATHOLOGY

AMER SOC INVESTIGATIVE PATHOLOGY, INC

Lugar: Bethesda ; Año: 2012 vol. 181 p. 1518 - 1523

0002-9440

Protein tyrosine phosphatase receptor type Z (Ptprz) is widely expressed in the mammalian central ner- vous system and has been suggested to regulate oligodendrocyte survival and differentiation. We in- vestigated the role of Ptprz in oligodendrocyte re- myelination after acute, toxin-induced demyelina- tion in Ptprz null mice. We found neither obvious impairment in the recruitment of oligodendrocyte precursor cells, astrocytes, or reactive microglia/mac- rophage 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 walle- rian 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 cen- tral nervous system axonal integrity in a demyelinat- ing environment and may be an important target of axonal protection in inflammatory demyelinating dis- eases, such as multiple sclerosis and periventricular leukomalacia.