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[P73]: Dysmyelination does not prevent normal cytoskeletal phosphorylation during development, but probably leaves axons vulnerable to later injury
Author(s) -
McCowan C.I.,
Slocombe R.F.,
Ayers M.M.,
Orian J.M.
Publication year - 2006
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2006.09.135
Subject(s) - cytoskeleton , phosphorylation , microbiology and biotechnology , neuroscience , chemistry , biology , biochemistry , cell
Myelin formation appears to be critical for both axonal maturity, represented by phosphorylation of neurofilament subunits, and subsequent axonal integrity. Formation of compact myelin appears to be a trigger for cytoskeletal change, but oligodendrocyte contact with the axon may not be required. Alterations in neurofilament phosphoforms, and accumulation of neurofilament subunits in axons, have been associated with neurodegenerative diseases, and accumulation of unphosphorylated neurofilament units is recognised as a marker of axonal injury in multiple sclerosis. We undertook investigations to evaluate the potential for recovery of oligodendrocyte numbers following significant precursor loss and the maturity of axonal neurofilaments and presence of axonal injury in relationship to myelination. The 2–50 tg mouse is a dysmyelinating mutant that suffers from early oligodendrocyte loss and subsequent hypomyelination. Optic nerves from normal and hemizygous transgenic 2–50 mice at 29 days and 120 days of age were examined for glial numbers and neurofilament phosphorylation. Using anti-CC1, S100 and GFAP antibodies to identify mature macroglia, we found that, although cell numbers are consistently lower for transgenic mice, the differences are not significant. Labelling with antibodies against myelin basic protein to show myelinated regions, and phosphorylated (SMI 31) or unphosphorylated (SMI 32) neurofilaments showed that neurofilament phosphorylation occurred even where detectable myelin was lacking. Accumulation of unphosphorylated neurofilaments was seen at the margins of unmyelinated regions in 120 day tg animals, but not in 29 day tg or in any non transgenic animals. The 2–50 tg mouse recovers to normal levels of glial cells in the optic nerve following oligodendrocyte loss. The axonal cytoskeleton is modified in the same fashion as in normal animals, despite areas of axons lacking myelin, but these areas show signs of degeneration by 120 days of age as indicated unphosphorylated neurofilament accumulation.