Early urinary candidate biomarkers in a rat model of experimental autoimmune encephalomyelitis

Abstract

AbstractBiomarker is the change associated with the disease. Without homeostatic control, urine can accumulate early changes in the body. We expect that urinary proteome can also reflect early changes in the nervous system and urine is a better biomarker source for nervous system diseases. Multiple sclerosis is a chronic autoimmune demyelinating disease of the central nervous system and is difficult to diagnose in early stages. In this study, a tandem mass labeling approach coupled with high-resolution mass spectrometry was used to analyze seven-day urinary proteome changes in a rat model of experimental autoimmune encephalomyelitis when the clinical scores in the EAE group were “0” and no obvious histological changes were observed. Thirty-one urinary proteins were altered, based on Ingenuity Pathway Analysis, seventeen of these proteins were associated with neurological functions. The top canonical pathways represented by these dysregulated proteins included the acute phase response and metabolic processes. The acute phase response was characterized by an increase in inflammatory factors that are known to cause multiple sclerosis. Additionally, lipid or glucose metabolic alterations may provide clues for future mechanistic studies on multiple sclerosis. Fourteen proteins were identified to have catalytic activities that may contribute to neuronal damage. Furthermore, among the seven proteins that were most affected, six were reported to be expressed in the serum/cerebrospinal fluid/brain tissue of multiple sclerosis patients, thereby indicating that urine can be a good source of biomarkers for the early detection of multiple sclerosis.