Spontaneous central nervous system remyelination is not altered in NFH-lacZ transgenic mice after chemical demyelination.
Harmonious functioning of the nervous system depends on neuron-glia interactions, particularly between the axons and their myelinating cells, i.e., oligodendrocytes (OL) in the central nervous system (CNS). In human demyelinating diseases such as multiple sclerosis (MS), demyelination may be associated with axonal damage, but alterations of the axonal cytoskeleton, which is composed mainly of neurofilaments (NF) and microtubules, are largely unknown, as are the consequences on remyelination. In a model of demyelination induced by lysophosphatidylcholine (LPC), we have shown that demyelination was correlated with a decrease in NF immunolabelling, and that these axonal abnormalities were reduced by platelet-derived growth factor (PDGF)-enhanced remyelination in adult rats. We have analysed the spontaneous remyelination after LPC stereotaxic injection in the CNS of transgenic NFH-lacZ mice, which present axonal atrophy caused by abnormal distribution of NF, associated with hypermyelination in the PNS, and normal myelin thickness in the CNS. Axonal atrophy in the CNS of NFH-lacZ mice was confirmed, but it was not worsened by demyelination. On the contrary, demyelination induced axonal atrophy in wild-type mice, demonstrating that NF are essential for axonal calibre determination. Moreover, an efficient spontaneous remyelination occurred in NFH-lacZ as well as in wild-type mice, indicating that the NF are not necessary for CNS remyelination. These findings point out that NF modifications observed in MS may not be responsible for the lack of remyelination in this disease.
Jean
Isabelle
I
Cell Biology Laboratory, UPRES EA 3143, University Hospital, Angers, France. isabelle.jean@med.univ-angers.fr
Fressinaud
Catherine
C
D000818:Animals; D001284:Atrophy; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology*; D007763:Lac Operon; D008244:Lysophosphatidylcholines; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology*; D016900:Neurofilament Proteins / Q000235:genetics*; D012075:Remission, Spontaneous
D008244:Lysophosphatidylcholines; D016900:Neurofilament Proteins; C051774:neurofilament protein H