RESEARCH: HSP--cellular findings in PLP gene

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Oligodendroglial modulation of fast axonal transport

in a mouse model of hereditary spastic paraplegia.

Edgar JM, McLaughlin M, Yool D, Zhang SC, Fowler JH,

Montague P, Barrie JA, McCulloch MC, Duncan ID,

Garbern J, Nave KA, Griffiths IR.

Applied Neurobiology Group, Dept. of Veterinary

Clinical Studies, University of Glasgow, Bearsden,

Glasgow G61 1QH, Scotland, UK.

I.Griffiths@...

Oligodendrocytes are critical for the development of

the plasma membrane and cytoskeleton of the axon. In

this paper, we show that fast axonal transport is also

dependent on the oligodendrocyte. Using a mouse model

of hereditary spastic paraplegia type 2 due to a null

mutation of the myelin Plp gene, we find a progressive

impairment in fast retrograde and anterograde

transport. Increased levels of retrograde motor

protein subunits are associated with accumulation of

membranous organelles distal to nodal complexes. Using

cell transplantation, we show categorically that the

axonal phenotype is related to the presence of the

overlying Plp null myelin. Our data demonstrate a

novel role for oligodendrocytes in the local

regulation of axonal function and have implications

for the axonal loss associated with secondary

progressive multiple sclerosis.

SOURCE: J Cell Biol. 2004 Jun 28 [Epub ahead of

print]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

5226307 & dopt=Abstract