title: Mice lacking urea transporter UT-B display depression-like behavior.
abstract: Urea transporter B is one of urea transporters that selectively transport urea driven by urea gradient across membrane and expressed abundantly in brain. To determine the physiological role of UT-B in brain, UT-B localization, urea concentration, tissue morphology of brain, and behavioral phenotypes were studied in UT-B heterozygous mice via UT-B null mice. UT-B mRNA was expressed in olfactory bulb, cortex, caudate nucleus, hippocampus and hypothalamus of UT-B heterozygous mice. UT-B null mice exhibited depression-like behavior, with urea accumulation, nitric oxide reduction, and selective neuronal nitric oxide synthase level increase in hippocampus. After acute urea loading, the urea level increased, NO production decreased in hippocampus from both types of mice. Moreover, urea level was higher, and NO concentration was lower consistently in UT-B null hippocampus than that in heterozygous hippocampus. In vitro, 25 mM urea inhibited NO production too. Furthermore, UT-B knockout induced a long-lasting notable decrease in regional cerebral blood flow and altered morphology, such as loss of neurons in CA3 region, swelling, and membranous myelin-like structure formation within myelinated and unmyelinated fibers in hippocampus. These results suggest that urea accumulation in the hippocampus induced by UT-B deletion can cause depression-like behavior, which possibly attribute to disturbance in NOS/NO system.
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Lu, Haidian District, Beijing, 100191, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Jianhua
authors.initials: J
authors.lastname: Ran
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Tianluo
authors.initials: T
authors.lastname: Lei
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Jingyan
authors.initials: J
authors.lastname: Han
authors.forename: Baoxue
authors.initials: B
authors.lastname: Yang
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation / Q000235:genetics; D003433:Crosses, Genetic; D003863:Depression / Q000235:genetics* / Q000503:physiopathology; D004924:Escape Reaction / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology; D005518:Food Preferences / Q000502:physiology; D005838:Genotype; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D026901:Membrane Transport Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009412:Nerve Fibers / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D014508:Urea / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C452857:urea transporter B, mouse; D009569:Nitric Oxide; D014508:Urea