[Abstract Title]. - Society for Neuroscience

neuropathy characterized by myelin degradation, Schwann cell dedifferentiation and
proliferation, and a reduction in nerve conduction velocity. The observed demyelination is
mediated by endoneurial accumulation of the substrate of the PAP1 enzyme, phosphatidic acid
(PA). Our results therefore reveal a surprising role for PA in Schwann cell fate determination and
provide evidence of a direct link between diseases affecting lipid metabolism and abnormal
Schwann cell function.
Disclosures: K. Nadra, None; R. Chrast , None; A. De Preux Charles, None; J. Médard,
None; W.T. Hendriks, None; M.H.G. Verheijen, None; G. Han, None; G.M. Carman,
None; S. Grès, None; J. Saulnier-Blache, None.
Poster
251. Demyelinating Disorders: Animal Models and Human Studies I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 251.15/W8
Topic: C.08.b. Animal models
Title: Chronic installation of lysophosphatidylcholine (c24:0) induces demyelination
Authors: *K. J. GAROFALO 1 , J.-Q. REN 1 , D. KULJIS 1 , R. RANSOHOFF 2 , F. EICHLER 1 ;
1 Mass Gen Hosp, Charlestown, MA; 2 Neuroinflam. Res. Ctr., Learner Res. Inst., Cleveland, OH
Abstract: We previously reported that intracerebral injections of very long chain fatty acids
(VLCFA) incorporated into lysophosphatidylcholine (LPC) induce microglial apoptosis in rodent
brain. Elevations in VLCFA occur in patients with X-linked adrenoleukodystrophy (ALD) and
may play a role in the pathogenesis of cerebral demyelination. In the current study we assess the
impact of chronic LPC (C24:0) exposure upon brain myelin and microglia in rodents. We
compared a one time stereotactic injection of LPC (C24:0) versus PBS with repeated injections
of LPC (C24:0) versus PBS (4 injections every 4 days). Mice injected only once were assessed
after 4 days and 3 weeks, and mice with repeated injections were assessed after 3 weeks only.
Repeated LPC (C24:0) injections induced microglial apoptosis and demyelination at three weeks.
By contrast, four days after a one-time injection of LPC (C24:0), but not PBS, microglial
activation and apoptosis was present without evidence of demyelination. Three weeks after a one
time exposure brain tissue had healed completely. We conclude that chronic LPC (C24:0)
exposure is necessary to induce cerebral demyelination. Following a one-time injection, brain
myelin is not affected and in the absence of repeated exposure complete healing can occur. The
data support the notion that lipid-reducing measures may alleviate the pathology in cerebral
ALD.