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Mice Lacking Urea Transporter UT-B Display Depression-Like Behavior

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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.

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Acknowledgements

This work was supported by National Natural Science Foundation of China grant 30870921 and 30500171, 985 Projects of Ministry of Education of China 985-2-094-121, Drug Discovery Program grant 2009ZX09301-010-30, Doctoral Training Fund 20100001110047, and Beijing Natural Science Foundation grant 7102105.

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  1. Department of Pharmacology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Lu, Haidian District, Beijing, 100191, China

    Xin Li, Hong Zhou, Tianluo Lei, Li Zhou & Baoxue Yang

  2. Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China

    Xin Li, Hong Zhou, Tianluo Lei, Li Zhou & Baoxue Yang

  3. Department of Anatomy, Neuroscience Research Center, Basic Medical College, Chongqing Medical University, Chongqing, China

    Jianhua Ran

  4. Tasly Microcirculation Research Center, School of Basic Medical Sciences, Peking University, Beijing, China

    Jingyan Han

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  1. Xin Li
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  3. Hong Zhou
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Correspondence to Baoxue Yang.

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Li, X., Ran, J., Zhou, H. et al. Mice Lacking Urea Transporter UT-B Display Depression-Like Behavior. J Mol Neurosci 46, 362–372 (2012). https://doi.org/10.1007/s12031-011-9594-3

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