Abstract Details

Title Peptidoglycan Induces Nitrosative Injury and Primary Oligodendrogliopathy

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 175

Objective

Background BACKGROUND: We had previously shown that injection of LPS into white matter tracts of the CNS induces primary demyelination and resembles Type III oligodendrogliopathy. In this model, apoptosis of oligodendrocytes and loss of cellular markers of astrocytes precede the histological development of demyelination. Since the development of an autoimmune syndrome is often preceded by an exposure to a "danger signal" we examined if activation of other TLR ligands is capable of inducing nitrosative injury to oligodendrocytes in vitro and nitrosative mediated primary demyelination in vivo.

Design/Methods DESIGN/METHODS: Primary oligodendrocytes were cultured in vitro with peptidoglycan and the activation of nitric oxide synthase and injury to mitochondrial enzymes were determined . Adult rats were anesthetized and injected into the corpus callosum of soluble of peptidoglycan or saline. Animals were sacrificed at different time points and the development and examined by immunohistochemistry for the development of demyelination.

Results RESULTS: Culture of oligodendrocytes in vitro led to activation of nitric oxide synthase, increase in NO production and NO mediated mitochondrial injury. Injection of peptidoglycan into the white matter tracts leads to a rapid loss of oligodendrocyte and the accumulation of tyrosninated proteins in oligodendrocytes which co-localized to oligodendrocytes undergoing apoptosis. This was followed by the extensive development of demyelination in the corpus callosum.

Conclusions CONCLUSIONS: Our study shows that activation of the NOD/2 ligand of PGN, leads to the activation of NO in oligodendrocytes and accumulation of nitrosative products. Injection of PGN in vivo led to the development of primary demyelination and accumulation of nitrotyrosine in oligodendroctyes. Demyelination mediated by PGN shows similarities to primary oligodendrogliopathy seen in MS and hence is a model of primary oligodendrogliopathy.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
Fanglin Zhang, MD, PhD (Stanford Medical Center)	No disclosure on file
Subramaniam Sriram, MD (Vanderbilt University Medical Center)	Dr. Sriram has nothing to disclose.
Steven Galetta, MD, FAAN (NYU Langone Medical Center)	Dr. Galetta has nothing to disclose.

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