Urea transporters in the mammalian brain

Facilitative urea transporters encoded by two distinct genes: SLC14A2 (UT-A) and SLC14A1 (UT-B) facilitate movement of urea across plasma cell membranes and have been found in different locations within different tissues in various mammalian species – holding important physiological implications in the urine concentrating mechanism, urea nitrogen salvaging process, and increasing interest in the physiological role of urea in the aging brain and in neurodegenerative disease. Other studies have relatively recently reported increased brain urea levels in Alzheimer’s disease human brain tissue and increased levels of urea and urea transporter SLC14A1 transcript in a prodomal transgenic sheep model of Huntington disease. Comprehensive studies of UT-B transporters in the mammalian (rat, mouse, human, etc) brain investigating expression, abundance, and localization of UT-B in the brain, specific UT-B isoform(s) expressed in the brain, and regulation of UT-B in cell lines were undertaken. Such characterization of the precise nature of UT-B in the brain (i.e. aging and diseased state) is essential because very little is understood about UT-B in the brain and the important implications on brain health. Studies conducted in this research project using a range of techniques (i.e. endpoint PCR, Western blotting, and immunolocalization) have determined UT-B RNA expression increases in aging brain although likewise was not definitively shown for UT-B protein abundance, how UT-B is regulated in C6 astrocyte cell lines, and novel UT-B isoforms are present in human brain. Much more work remains to be done to determine the functional relevance of UT-B transporters and hence understand their physiological significance in the mammalian brain under physiological and diseased states.