Proteome analysis of brain in murine experimental autoimmune encephalomyelitis

Abstract

Multiple sclerosis is considered a prototype inflammatory autoimmune disorder of the CNS. Experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein is one of the best-characterized animal models of multiple sclerosis. Comprehensive understanding of gene expression in EAE can help identify genes that are important in drug response and pathogenesis. We applied a 2-DE-based proteomics approach to analyze the protein expression pattern of the brain in healthy and EAE samples. Of more than 1000 protein spots we analyzed, 70 showed reproducible and significant changes in EAE compared to controls. Of these, 42 protein spots could be identified using MALDI TOF-TOF-MS. They included mitochondrial and structural proteins as well as proteins involved in ionic and neurotransmitter release, blood barriers, apoptosis, and signal transduction. The possible role of these proteins in the responses of mice to animal models of multiple sclerosis is discussed.

Suppression of the Peripheral Immune System Limits the Central Immune Response Following Cuprizone-Feeding: Relevance to Modelling Multiple Sclerosis

“…In contrast to earlier work [49,91,97,99,135], this study used three technical replicates for each of the 5 biological replicates per experimental group, ensuring that only the most reproducible changes in proteoform abundance were assessed. Consequently, in contrast to the detection of ~700–1200 spots in previous studies [49,88,100,105], ~1650 protein spots per condition were resolved in this study.…”

“…Therefore, a quantitative ‘top-down’ proteomic approach was carried out to resolve protein species from whole brains of the CPZ-fed(±PT) mice. To date, proteome analyses of MS have mainly assessed tissue from late-stage post mortem brain samples and cerebrospinal fluid [89,96] or EAE animals [88,93,100,105]; these analyses provide useful insight into the ‘final readout’ of the disease or its autoimmune aspects [131,132,133] but not necessarily insight into the processes involved in disease aetiology and progression, including the role of oligodendrocytosis [1,49].…”

The protective role of TBX21-1514T>C polymorphism in susceptibility to multiple sclerosis

“… 6 Considering the autonomous activity of Th1 cells as one reason for MS, many evaluations have been done on T-bet transcription factor. As reported by Fazeli, et al, 7 increased expression of T-bet is demonstrated in the animal model contributed to MS disease, known as experimental autoimmune encephalomyelitis (EAE). Interestingly, T-bet-deficient mice are protected from EAE progression, 8 and T-bet silencing in vivo has shown inhibiting effects on EAE development; 9 thus confirming the necessity of T-bet encoding gene, TBX21, in MS pathogenesis.…”

Pleiotrophin Suppression of Receptor Protein Tyrosine Phosphatase-β/ζ Maintains the Self-Renewal Competence of Fetal Human Oligodendrocyte Progenitor Cells

“…Importantly, besides its autocrine production by OPCs, pleiotrophin is also expressed and secreted by human brain endothelial cells (Himburg et al, 2010), suggesting a role for the perivascular niche in dictating the self-renewal competence of resident OPCs (Goldman and Chen, 2011). In addition, astrocytes and microglia have also been reported to express pleiotrophin in experimental models of ischemic injury and demyelination (Yeh et al, 1998; Fazeli et al, 2010), suggesting that the widespread inactivation of PTPRZ1 activity in response to local stressors may serve to trigger the mobilization of resident progenitors.…”