Proteome analysis of spinal cord during the clinical course of monophasic experimental autoimmune encephalomyelitis

Abstract

The induction of autoimmune encephalomyelitis (EAE) in Lewis rats results in a period of exacerbation followed by complete recovery. Therefore, this model is widely used for studying the evolution of multiple sclerosis. In the present investigation, differentially expressed proteins in the spinal cord of Lewis rats during the evolution of EAE were assessed using the combination of 2DE and MALDI-TOF MS. The majority of the differentially expressed proteins were identified during the acute phase of EAE, in relation to naïve control animals. On the other hand, recovered rats presented a similar protein expression pattern in comparison with the naïve ones. This observation can be explained, at least in part, by the intense catabolism existent in acute phase due to nervous tissue damage. In recovered rats, we have described the upregulation of proteins that are apparently involved in the recovery of damaged tissue, such as light and medium neurofilaments, glial fibrillary acidic protein, tubulins subunits, and quaking protein. These proteins are involved mainly in cell growth, myelination, and remyelination as well as in astrocyte and oligodendrocyte maturation. The present study has demonstrated that the inflammatory response, characterized by an increase of the proliferative response and infiltration of autoreactive T lymphocytes in the central nervous system, occurs simultaneously with neurodegeneration.

How can proteomics elucidate the complexity of multiple sclerosis?

“…Nevertheless, EAE has been unequivocally important for understanding the neuroinflammatory mechanisms of multiple sclerosis. Moreover, recent studies using different proteomics approaches have noted early neurodegenerative signatures during the evolution of EAE , which seems to be, at least in part, in agreement with the findings in CSF from multiple sclerosis patients .…”

Vitamin D3 Induces IDO+ Tolerogenic DCs and Enhances Treg, Reducing the Severity of EAE

“…Each animal received a subcutaneous injection of 50 μg gpMBP, purified from guinea pig brain, or 15 μg of gpMBP 73‐86 peptide (QKSQRSQDENPV), emulsified in complete Freund's adjuvant containing 2 mg/mL of Mycobacterium tuberculosis H37RA (Difco, Detroit, MI, USA). The clinical expression of the disease was graded on a clinical index scale 0–5 in accordance with previous work .…”

Albumin and multiple sclerosis

“…Since albumin is the predominant protein in plasma, it would be expected to be among the proteins that gain access to the CNS. For instance, proteomic [ 30 , 36 ], immunohistochemical [ 37 – 40 ], immunoblotting [ 41 ], Evan’s blue labeled albumin [ 42 ], CSF [ 43 , 44 ], and radiolabeled albumin [ 45 ] studies in EAE subjects revealed that albumin enters the CNS during disease. Albumin extravasation precedes both cellular inflammation and clinical signs, and it occurs initially around vessels, i.e., perivascular space in subpia, and then spreads diffusely into the CNS [ 38 ].…”