Early urinary candidate biomarkers and clinical outcomes of intervention in a rat model of experimental autoimmune encephalomyelitis

Abstract

Multiple sclerosis is a chronic autoimmune demyelinating disease of the central nervous system and is difficult to diagnose in early stages. Without homeostatic control, urine was reported to have the ability to accumulate early changes in the body. We expect that urinary proteome can reflect early changes in the nervous system. The early urinary proteome changes in a most employed multiple sclerosis rat model (experimental autoimmune encephalomyelitis) were analysed to explore early urinary candidate biomarkers, and early treatment of methylprednisolone was used to evaluate the therapeutic effect. Twenty-five urinary proteins were altered at day 7 when there were no clinical symptoms and obvious histological changes. Fourteen were reported to be differently expressed in the serum/cerebrospinal fluid/brain tissues of multiple sclerosis patients or animals such as angiotensinogen and matrix metallopeptidase 8. Functional analysis showed that the dysregulated proteins were associated with asparagine degradation, neuroinflammation and lipid metabolism. After the early treatment of methylprednisolone, the incidence of encephalomyelitis in the intervention group was only 1/13. This study demonstrates that urine may be a good source of biomarkers for the early detection of multiple sclerosis. These findings may provide important information for early diagnosis and intervention of multiple sclerosis in the future.