Journal Article

Monitoring of experimental autoimmune encephalomyelitis pathways during pharmacological modulation

Saborio, G, Vignaud, C, Zanoguera, F, Nock, S, Wojcik, J, Vitte, P-A, Carboni, S, Peixoto, H, Abderrahim, H, Curchod, M L, Lamarine, M, Salvat, C

2008

Overview

Background: Multiple sclerosis (MS) is a complex disease with a mul tifaceted etiology and heterogeneous pathology. Demyelinated central nervous system (CNS) lesions are the pathologic hallmark of MS and are accompanied by inflammation, reactive gliosis, oligodendro cyte death and axonal loss. Experimental autoimmune encephalomyelitis (EAE) is widely used as an animal model of MS, serving as a valuable tool to study the pathogenesis and test new therapeutic approaches. Objective: The aim is to characterize the gene expression profile in different tissues of MOG-induced EAE in CS7B/6 mice covering different states of the disease. This genomics paradigm enables an extensive concurrent representation of genes and pathways relevant to the pathological and drug treatment processes. Methods: The gene expression profile, characterizing the progression of EAE was studied by microarray analysis following temporal progression (7, 10, 14, 21 and 28 days) after disease induction. RNA from several tissues, CNS areas (spinal cord and cerebellum) lymph nodes, spleen and blood was studied in four individual mice with homogeneous clinical score per time point. The involvement of specific biological pathways and the over and under-representation of biological functions have been investigated by different analysis approaches including hierarchical clustering and pathway analysis. Results: We performed a stepwise analysis. First, at the gene level we observed that the total number of regulated genes was time and clinical score-dependent. Then, the predominant canonical pathways were identified at each time point to characterize the main physiopathological mechanisms taking place during disease progression. The next step involved identifying modulated pathways in the same model and tissues in animals receiving pharmacological treatment with recognized mode of action. Examples of such modulated pathways are discussed. Conclusions: We have developed a useful and valuable tool for monitoring pathways in disease models, which can be used to characterize the pharmacological modulation of candidate targets and profile compounds.