Neuropathy Research Abstracts
Laminin Reverses
the Neurotoxicity of Sera From Patients With Neuropathy.
Gary L. Pittenger*, Nina Burcus, Aaron I. Vinik*,
Norfolk, VA.
Sera from patients with diabetic
neuropathy exert neurotoxicity on N1E-115 neuroblastoma cells (NB) by an autoimmune
induction of apoptosis that correlates with sensory dysfunction. There is a
down-regulation of laminin gene expression in sensory dorsal root ganglion neurons in
streptozotocin diabetic rats. Since upregulation of both laminin and its b 2 subunit are
associated with enhanced neurite outgrowth, we tested the possibility that laminin might
reverse the neurotoxicity of patient sera. NB were cultured for 4 days in DMEM
supplemented with 10% of either pooled human serum (PHS, Sigma) or patient test sera
selected for their neurotoxicity. Another set of identical cultures were treated with 20m
g/ml laminin. There was no signficant effect of laminin on PHS treated cultures (88,833±
76,314, mean increment ± SEM on day 4 of culture). Of 18 patients’ sera tested,
neurotoxicity was reversed in 14 cultures treated with toxic sera, including sera from
IDDM (663,6851 132,970,n=7), NIDDM (744,688± 29,688, n=5) or non-diabetic neuropathy
(707,250± 101,829, n=6) patients (p<0.02, ANOVA). Sera that failed to reverse toxicity
with 20m g/ml were tested with doses of 100 and 50 m g/ml of laminin to test whether
higher doses might overcome toxicity. A dose-dependent response was detected in cultures
treated with these sera, although there was not a return to the levels found in
"responders." Tests with equimolar amounts of the b 1 chain of laminin showed an
ability to reverse neurotoxicity in a subset of "responders," but was not able
to completely mimic the effects of the whole laminin molecule.
These data indicate that impaired
laminin gene expression might favor development of sensory neuropathy induced by
serum-mediated apoptosis, correctible in vitro with exogenous laminin. Thus, laminin might
be an important neurotrophic factor for the reversal of neuropathy, not just in diabetes
but also in other forms of autoimmune neuropathy.
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