Expression of Urea Transporter B in Normal and Injured Brain

Abstract

Urea transporter B (UT-B) is a membrane channel protein widely distributed in mammals, and plays a significant physiological role by regulating urea and water transportation in different tissues. More and more studies have found that UT-B is related to neurological diseases, including myelinopathy and depression. When urea accumulates in the brains of UT-B knockout mice, the synaptic plasticity of neurons is reduced, and the morphology and function of glial cells are also changed. However, the distribution and expression change of UT-B remain unclear. The purpose of this study is to determine the expression characteristics of UT-B in the brain. Through single-cell RNA sequencing, UT-B was found to express universally and substantially throughout the various cells in the central nervous system except for endothelial and smooth muscle cells. UT-B was detected in the third cerebral ventricular wall, granule cell layer of the dentate gyrus, and other parts of the hippocampal, cerebral cortex, substantia nigra, habenular, and lateral hypothalamic nucleus by immunohistochemistry. Compared with the membrane expression of UT-B in glial cells, the subcellular localization of UT-B is in the Golgi apparatus of neurons. Further, the expression of UT-B was regulated by osmotic pressure in vitro. In the experimental traumatic brain injury model (TBI), the number of UT-B positive neurons near the ipsilateral cerebral cortex increased first and then decreased over time, peaking at the 24 h. We inferred that change in UT-B expression after the TBI was an adaptation to changed urea levels. The experimental data suggest that the UT-B may be a potential target for the treatment of TBI and white matter edema.

Nuclear Magnetic Resonance Spectroscopy Metabolomics in Idiopathic Intracranial Hypertension to Identify Markers of Disease and Headache

“…33 Traumatic brain injury (TBI) models in mice have also demonstrated alterations in the expression of urea transporters, which was believed to be an adaptive modulation for changing urea levels. 34 Of interest, we also demonstrated a negative relationship between CSF urea and headache severity (with high CSF urea being associated with increased headache severity). These findings suggest that alteration of the CSF:serum urea gradient in IIH may be important in driving headache (Figure 4).…”

“… 33 Traumatic brain injury (TBI) models in mice have also demonstrated alterations in the expression of urea transporters, which was believed to be an adaptive modulation for changing urea levels. 34 …”

“…2 of which were increased to concentrations akin to controls, including glycylproline (baseline 55. 36…”

Regional investigation of UT-B urea transporters in the rat brain

“…This outcome is further consolidated by the lack of staining reported here in immunolocalization experiments, in which robust staining corresponding to UT-B was restricted the red blood cells within cerebellum blood vessels. Recent studies have detailed UT-B in rat brain in the third cerebral ventricular wall, granule cell layer of the dentate gyrus, and other parts of hippocampus, cerebral cortex, substantia nigra, habenular, and lateral hypothalamic nucleus [ 5 ]. Therefore, the lack of other specific staining patterns in the anterior, posterior and cerebellum regions in the current study was somewhat surprising.…”

“…UT-B was first identified as the primary brain urea transporter when it was cloned from rat brain tissue [ 3 ]. Since then, UT-B protein expression has been reported in various other mammalian brains – including mice [ 4 ] and humans [ 5 ]. UT-B is believed to be essential for maintaining urea concentration in the central nervous system and may be important in balancing sodium and water in cerebrospinal fluid [ 6 ].…”