Biomarkers are the measurable changes associated with a physiological or pathophysiological process. Unlike blood, urine is not subject to homeostatic mechanisms. Therefore, greater fluctuations could occur in urine than in blood, better reflecting the changes in human body. The roadmap of urine biomarker era was proposed. Although urine analysis has been attempted for clinical diagnosis, and urine has been monitored during the progression of many diseases, particularly urinary system diseases, whether urine can reflect brain disease status remains uncertain. As some biomarkers of brain diseases can be detected in the body fluids such as cerebrospinal fluid and blood, there is a possibility that urine also contain biomarkers of brain diseases. This review summarizes the clues of brain diseases reflected in the urine proteome and metabolome.

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Biomarkers are the measurable changes associated with a physiological or pathophysiological process. The content of urine frequently changes because it is not controlled by homeostatic mechanisms, and these alterations can be a source of biomarkers. However, urine is affected by many factors. In this study, vasoconstrictor and antidiuretic arginine vasopressin (AVP) were infused into rats using an osmotic pump. The rats’ urinary proteome after one week of infusion was analyzed by label-free LC-MS/MS. A total of 408 proteins were identified; among these proteins, eight and 10 proteins had significantly altered expression in the low and high dose groups, respectively, compared with the control group using the one-way ANOVA analysis followed by post hoc analysis with the least significant difference (LSD) test or Dunnett’s T3 test. Three differential proteins were described in prior studies as related to AVP physiological processes, and nine differential proteins are known disease biomarkers. Sixteen of the 17 differential proteins have human orthologs. These results suggest that we should consider the effects of AVP on urinary proteins in future urinary disease biomarker researches. The study data provide clues regarding underlying mechanisms associated with AVP for future physiological researches on AVP. This study provide a sensitive changes associated with AVP. However, the limitation of this result is that the candidate biomarkers should be further verified and filtered. Large clinical samples must be examined to verify the differential proteins identified in this study before these proteins are used as biomarkers for pathological AVP increased diseases, such as syndrome of inappropriate antidiuretic hormone secretion (SIADH).

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