Neuroprotective effect of a synapsin peptide genetically fused to the B subunit of Escherichia coli heat-labile enterotoxin in rat autoimmune encephalomyelitis

M. JULIA SCERBO; LUCÍA L. RUPIL; MARIO J. BIBOLINI; GERMAN A. ROTH; CLARA G. MONFERRAN

JOURNAL OF NEUROSCIENCE RESEARCH

Wiley-Liss

Año: 2009 vol. 87 p. 2273 - 2281

0360-4012

       Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease with similarities to multiple sclerosis that requires the activation of auto reactive T cells that infiltrate the central nervous system. In previous studies we have shown that intraperitoneal administration of synaptosomal antigens could suppress EAE. Herein we examined the effect in this animal model of a fusion protein comprising the C domain of synapsin Ia and the B subunit of Escherichia coli heat-labile enterotoxin (LTBSC). Oral administration to rats of low amount of LTBSC induced immunological systemic tolerance to the encephalitogenic myelin basic protein. Treatment with LTBSC prior to EAE induction diminished disease incidence, DTH reaction to myelin basic protein and central nervous system inflammation. LTBSC treatment also reduced the specific T-cell proliferative response to myelin basic protein, and decreased nitric oxide production and augmented arginase activity by peritoneal macrophages. All animals challenged for EAE developed antibody response specific for myelin basic protein but rats treated with LTBSC showed lower IgG2b/IgG1 ratio indicating a shift to a Th2 type milieu. The data herein presented suggest that well conserved-synapsin peptides conjugated to the B subunit of enterotoxins from the cholera toxin family have a protective role and provide a potential therapeutic tool for intervention in EAE as well as in multiple sclerosis.