[Abstract Title]. - Society for Neuroscience

protein kinase cascade MEK1/2-ERK1/2 as an important mediator of MCP-1 expression in
mutant Schwann cells. To elucidate if MCP-1 has a common role in mouse models for other
CMT1-forms, we examined the function of MCP-1 in peripheral myelin protein 22
overexpressing mice (PMP22tg, C61) and mice deficient in connexin32 (Cx32-/-), which are
models for CMT1A and for the X-linked, dominant form of CMT1 (CMT1X), respectively. We
crossbred PMP22tg and the Cx32-/- mice with MCP-1 mutants and used immunohistochemistry,
electron microscopy, real-time PCR and western blots for analyses of single and double mutant
animals. Similarly to the findings in P0+/-mice, femoral quadriceps nerves of 6 months old
PMP22tg/MCP-1+/- and Cx32-/-/MCP-1+/- mice showed reduced numbers of macrophages and
exhibited a significant amelioration of the pathological phenotype. Peripheral nerves of
PMP22tg/MCP-1-/- mice showed also reduced numbers of macrophages but alleviation was not
as striking as in PMP22tg/MCP-1+/- mice. Contrary, peripheral nerves of Cx32-/-/MCP-1-/-
showed similar to P0+/-/MCP-1-/- mice an aggravation of disease, accompanied by only slightly
reduced numbers of macrophages in comparison to Cx32-/-/MCP-1+/-. Thus, reduction but not
complete absence of MCP-1 substantially alleviates the pathological phenotype in three distinct
mouse models for CMT1. The search for regulatory pathways of MCP-1-upregulation in
PMP22tg and Cx32-/- mice, identified ERK1/2 in the PMP22tg mice, whereas in Cx32-/- mice
MCP-1 might be upregulated independently from ERK1/2. Our findings show that the
expression of MCP-1 is crucial for the pathological mechanisms in three mouse models for
CMT1, whereas the regulation of MCP-1 expression might require different intracellular
pathways.
Disclosures: B.D. Kohl , None; S.M. Fischer, None; J. Groh, None; A. Weishaupt, None; J.
Troppmair, None; R. Martini, None.
Poster
252. Demyelinating Disorders: Mechanisms and Therapeutics II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 252.7/W31
Topic: C.08.d. Therapeutic strategies
Support: National Multiple Sclerosis Society
Title: Low dose naltrexone (LDN) and opioid growth factor (OGF) prevent or delay
experimental autoimmune encephalomyelitis (EAE)
Authors: *K. A. RAHN 1 , R. H. BONNEAU 2 , P. J. MCLAUGHLIN 1 , I. S. ZAGON 1 ;
1 Neural & Behavioral Sci., 2 Microbiology & Immunol., Penn State Univ. Coll Med., Hershey,
PA