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Deletion of mouse FXR gene disturbs multiple neurotransmitter systems and alters neurobehavior
Open accessAbstract
Farnesoid X receptor (FXR) is a nuclear hormone receptor involved in bile acid synthesis and homeostasis. Dysfunction of FXR is involved in cholestasis and atherosclerosis. FXR is prevalent in liver, gallbladder, and intestine, but it is not yet clear whether it modulates neurobehavior. In the current study, we tested the hypothesis that mouse FXR deficiency affects a specific subset of neurotransmitters and results in an unique behavioral phenotype. The FXR knockout mice showed less depressive-like and anxiety-related behavior, but increased motor activity. They had impaired memory and reduced motor coordination. There were changes of glutamatergic, GABAergic, serotoninergic, and norepinephrinergic neurotransmission in either hippocampus or cerebellum. FXR deletion decreased the amount of the GABA synthesis enzyme GAD65 in hippocampus but increased GABA transporter GAT1 in cerebral cortex. FXR deletion increased serum concentrations of many bile acids, including taurodehydrocholic acid, taurocholic acid, deoxycholic acid (DCA), glycocholic acid (GCA), tauro-α-muricholic acid, tauro-ω-muricholic acid, and hyodeoxycholic acid (HDCA). There were also changes in brain concentrations of taurocholic acid, taurodehydrocholic acid, tauro-ω-muricholic acid, tauro-β-muricholic acid, deoxycholic acid, and lithocholic acid (LCA). Taken together, the results from studies with FXR knockout mice suggest that FXR contributes to the homeostasis of multiple neurotransmitter systems in different brain regions and modulates neurobehavior. The effect appears to be at least partially mediated by bile acids that are known to cross the blood-brain barrier (BBB) inducing potential neurotoxicity.
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“FXR knockout mice exhibit abnormal BA and neurotransmitter concentrations, resulting in impaired cognition and motor coordination (304).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [304]
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Cites
Metabotropic Glutamate Receptors: Physiology, Pharmacology, and Disease
Niswender, C. M., & Conn, P. J. (2010) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.011008.145533 · Cited by 1,889
Targeted Disruption of the Nuclear Receptor FXR/BAR Impairs Bile Acid and Lipid Homeostasis
Sinal, C. J., Tohkin, M., Miyata, M., Ward, J. M., Lambert, G., & Gonzalez, F. J. (2000) · Cell · doi:10.1016/s0092-8674(00)00062-3 · Cited by 1,819
Identification of a nuclear receptor that is activated by farnesol metabolites
Forman, B. M., Goode, E., Chen, J., Oro, A. E., Bradley, D. J., Perlmann, T., Noonan, D. J., Burka, L. T., McMorris, T., Lamph, W. W., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90530-8 · Cited by 1,210
Identification of membrane-type receptor for bile acids (M-BAR)
Maruyama, T., Miyamoto, Y., Nakamura, T., Tamai, Y., Okada, H., Sugiyama, E., Nakamura, T., Itadani, H., & Tanaka, K. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)02550-0 · Cited by 993
The GABAergic deficit hypothesis of major depressive disorder
Luscher, B., Shen, Q., & Sahir, N. (2011) · Molecular Psychiatry · doi:10.1038/mp.2010.120 · Cited by 934
Bile acids as regulatory molecules
Hylemon, P. B., Zhou, H., Pandak, W. M., Ren, S., Gil, G., & Dent, P. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r900007-jlr200 · Cited by 694
Nuclear Receptor-Dependent Bile Acid Signaling Is Required for Normal Liver Regeneration
Huang, W., Ma, K., Zhang, J., Qatanani, M., Cuvillier, J., Liu, J., Dong, B., Huang, X., & Moore, D. D. (2006) · Science · doi:10.1126/science.1121435 · Cited by 645
Sanacora, G., Mason, G. F., Rothman, D. L., Behar, K. L., Hyder, F., Petroff, O. A. C., Berman, R. M., Charney, D. S., & Krystal, J. H. (1999) · Archives of General Psychiatry · doi:10.1001/archpsyc.56.11.1043 · Cited by 627
Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine
Kim, I., Ahn, S.-H., Inagaki, T., Choi, M., Ito, S., Guo, G. L., Kliewer, S. A., & Gonzalez, F. J. (2007) · Journal of Lipid Research · doi:10.1194/jlr.m700330-jlr200 · Cited by 589
Magnetic Resonance Spectroscopy Studies of Glutamate-Related Abnormalities in Mood Disorders
Yüksel, Ç., & Öngür, D. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.06.016 · Cited by 493
Yang, F., Huang, X., Yi, T., Yen, Y., Moore, D. D., & Huang, W. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-1078 · Cited by 488
Crossing the barrier: oxysterols as cholesterol transporters and metabolic modulators in the brain
Björkhem, I. (2006) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2006.01725.x · Cited by 397
Seol, W., Choi, H.-S., & Moore, D. D. (1995) · Molecular Endocrinology · doi:10.1210/mend.9.1.7760852 · Cited by 389
Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice
Kim, I., Morimura, K., Shah, Y., Yang, Q., Ward, J. M., & Gonzalez, F. J. (2007) · Carcinogenesis · doi:10.1093/carcin/bgl249 · Cited by 357
Facilitation of glutamate receptors enhances memory.
Staubli, U. V., Rogers, G. A., & LYNCH, G. S. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.2.777 · Cited by 330
Asada, H., Kawamura, Y., Maruyama, K., Kume, H., Ding, R.-G., Ji, F. Y., Kanbara, N., Kuzume, H., Sanbo, M., Yagi, T., et al. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1898 · Cited by 315
Anxiety-Related Behaviors in Mice
Crawley, J. N., & Bailey, K. (2008) · Frontiers in neuroscience · doi:10.1201/noe1420052343.ch5 · Cited by 277
Quinn, M., McMillin, M., Galindo, C., Frampton, G., Pae, H. Y., & DeMorrow, S. (2014) · Digestive and Liver Disease · doi:10.1016/j.dld.2014.01.159 · Cited by 259
Evaluating the Affective Component of the Cerebellar Cognitive Affective Syndrome
Wolf, U., Rapoport, M. J., & Schweizer, T. A. (2009) · Journal of Neuropsychiatry · doi:10.1176/jnp.2009.21.3.245 · Cited by 209
Farnesoid X Receptor Regulates Bile Acid-Amino Acid Conjugation
Pircher, P. C., Kitto, J. L., Petrowski, M. L., Tangirala, R. K., Bischoff, E. D., Schulman, I. G., & Westin, S. K. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302128200 · Cited by 197
Benefit of farnesoid X receptor inhibition in obstructive cholestasis
Stedman, C. A. M., Liddle, C., Coulter, S., Sonoda, J., Alvarez, J. G. A., Evans, R. M., & Downes, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604772103 · Cited by 171
Inhibition of γ-aminobutyric acid uptake: anatomy, physiology and effects against epileptic seizures
Dalby, N. O. (2003) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2003.08.063 · Cited by 170
Cherlyn, S. Y. T., Woon, P. S., Liu, J., Ong, W., Tsai, G., & Sim, K. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.01.002 · Cited by 165
Effects of feeding bile acids and a bile acid sequestrant on hepatic bile acid composition in mice
Zhang, Y., & Klaassen, C. D. (2010) · Journal of Lipid Research · doi:10.1194/jlr.m007641 · Cited by 146
Glutamatergic and gabaergic neurotransmission and neuronal circuits in hepatic encephalopathy
Cauli, O., Rodrigo, R., Llansola, M., Montoliu, C., Monfort, P., Piedrafita, B., Mlili, N. E., Boix, J., Agustí, A., & Felipo, V. (2008) · Metabolic Brain Disease · doi:10.1007/s11011-008-9115-4 · Cited by 144
Effects of FXR in foam-cell formation and atherosclerosis development
Guo, G. L., Santamarina-Fojo, S., Akiyama, T. E., Amar, M. J., Paigen, B. J., Brewer, B., & Gonzalez, F. J. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2006.09.018 · Cited by 133
Animal models concerning the role of dopamine in attention-deficit hyperactivity disorder
van der Kooij, M. A., & Glennon, J. C. (2007) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2006.12.002 · Cited by 128
Magen, I., Avraham, Y., Ackerman, Z., Vorobiev, L., Mechoulam, R., & Berry, E. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00589.x · Cited by 125
Eyles, D. W., Liu, P.-Y., Josh, P. F., & Cui, X. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.02.042 · Cited by 122
Bile acid signaling and liver regeneration
Fan, M., Wang, X., Xu, G., Yan, Q., & Huang, W. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.05.021 · Cited by 110
Yang, L., Xiong, A., He, Y., Wang, Z., Wang, C., Wang, Z., Li, W., Yang, L., & Zhi-bi, H. (2008) · Chemical Research in Toxicology · doi:10.1021/tx800225q · Cited by 104
Simultaneous quantification of seven hippocampal neurotransmitters in depression mice by LC–MS/MS
Huang, F., Li, J., Shi, H., Wang, T., Muhtar, W., Du, M., Zhang, B.-B., Wu, H., Yang, L., Zhi-bi, H., et al. (2014) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2014.04.004 · Cited by 92
He, Y., Du, M., Gao, Y. L., Liu, H., Wang, H., Wu, X., & Wang, Z. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076495 · Cited by 87
Yokota, S., Moriya, N., Iwata, M., Umezawa, M., Oshio, S., & Takeda, K. (2013) · The Journal of Toxicological Sciences · doi:10.2131/jts.38.13 · Cited by 78
Bjursell, M., Wedin, M., Admyre, T., Hermansson, M., Böttcher, G., Göransson, M., Lindén, D., Bamberg, K., Oscarsson, J., & Bohlooly‐Y, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064721 · Cited by 77
Monfort, P., Erceg, S., Piedrafita, B., Llansola, M., & Felipo, V. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05444.x · Cited by 75
de Villiers, A. S., Russell, V. A., Sagvolden, T., Searson, A., Jaffer, A., & Taljaard, J. J. F. (1995) · Neurochemical Research · doi:10.1007/bf00973098 · Cited by 73
Presynaptic Glutamatergic Dysfunction in Bipolar Disorder
Chen, G., Henter, I. D., & Manji, H. K. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.03.027 · Cited by 52
Akanuma, S.-I., Hori, S., Ohtsuki, S., Fujiyoshi, M., & Terasaki, T. (2008) · Neurochemistry International · doi:10.1016/j.neuint.2007.08.012 · Cited by 43
Kim, J. M., Kim, D. H., Lee, Y., Park, S. J., & Ryu, J. H. (2014) · Brain Research · doi:10.1016/j.brainres.2014.01.024 · Cited by 35
Jia, L., Jiang, D., Hu, P., Li, X., Shi, H., Cheng, D., & Zhang, L. (2014) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2014.03.016 · Cited by 30
Bueno-Nava, A., González-Piña, R., Alfaro-Rodríguez, A., Nekrassov-Protasova, V., Durand‐Rivera, A., Montes, S., & Ayala‐Guerrero, F. (2010) · Neurochemical Research · doi:10.1007/s11064-010-0213-4 · Cited by 26
Mania as the first manifestation of Wilson’s disease
Machado, A. C., Deguti, M. M., Caixeta, L. F., Spitz, M., Lucato, L. T., & Barbosa, E. R. (2008) · Bipolar Disorders · doi:10.1111/j.1399-5618.2007.00531.x · Cited by 24
Bueno-Nava, A., Montes, S., la Garza-Montaño, P. D., Alfaro-Rodríguez, A., Ortiz, A., & González-Piña, R. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.07.046 · Cited by 22
Pregnane X Receptor and P-glycoprotein: a connexion for Alzheimer’s disease management
Jain, S. K., Rathod, V. P., Prajapati, R., Nandekar, P. P., & Sangamwar, A. T. (2014) · Molecular Diversity · doi:10.1007/s11030-014-9550-6 · Cited by 21
Anxiety and depression propensities in patients with acute toxic liver injury
Suh, J. I. (2013) · World Journal of Gastroenterology · doi:10.3748/wjg.v19.i47.9069 · Cited by 21
Cardiac dynamics in corticotropin-releasing factor receptor subtype-2 deficient mice
Stiedl, O., & Meyer, M. (2003) · Neuropeptides · doi:10.1016/s0143-4179(02)00135-x · Cited by 17
Brain Ag-NOR activity in cholestatic rats with hepatic encephalopathy
García‐Moreno, L. M. (2002) · Hepatology Research · doi:10.1016/s1386-6346(02)00132-8 · Cited by 16
Anxiety-Related Behaviors in Mice -- Methods of Behavior Analysis in Neuroscience
Jj, B. (2009) · Cited by 15
[Anxiety level studies in patients with chronic liver diseases].
Ev, T., Nv, K., Korzhenevs'kyĭ, I. L., & Lopukh, I. I. (2013) · PubMed · Cited by 1
Дослідження рівня тривожності у хворих з хронічними захворюваннями печінки
Tkachenko, O. V., Kharchenko, N. V., Korzhenevskyy, Y. L., & Lopukh, I. Y. (2013) · Likarska sprava · doi:10.31640/ls-2013-5-08 · Cited by 1
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Bile acid signaling pathways from the enterohepatic circulation to the central nervous system
Mertens, K. L., Kalsbeek, A., Soeters, M. R., & Eggink, H. M. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00617 · Cited by 287
Gut microbial metabolites in depression: understanding the biochemical mechanisms
Caspani, G., Kennedy, S. H., Foster, J. A., & Swann, J. R. (2019) · Microbial Cell · doi:10.15698/mic2019.10.693 · Cited by 289
Effects of bile acids on neurological function and disease
McMillin, M., & DeMorrow, S. (2016) · The FASEB Journal · doi:10.1096/fj.201600275r · Cited by 192
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Metadata
- Authors
- Huang, F., Wang, T., Lan, Y., Yang, L., Pan, W., Zhu, Y., Lv, B., Wei, Y., Shi, H., Wu, H., Zhang, B., Wang, J., Duan, X., Hu, Z., & Wu, X.
- Affiliations
- Shanghai University of Traditional Chinese Medicine (CN)
- Pennington Biomedical Research Center (US)
- Shanghai East Hospital (CN)
- Corresponding author
- Wu, Xiaojun
- ORCID
- Venue
- Frontiers in Behavioral Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2015-03-30
- Volume
- 9
- Pages
- 70-70
- ISSN
- 1662-5153 (ISSN-L)
- PMC
- PMC4378301
- OpenAlex
- W2151789409
- Cited by
- 109
- References
- 52
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 21 · 2023: 8 · 2022: 18 · 2021: 10 · 2020: 8 · 2019: 6 · 2018: 6 · 2017: 3 · 2016: 6
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Behavioral Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- farnesoid X receptor, FXR knockout mice, bile acids, neurotransmitter systems, neurobehavior, depression-like behavior, anxiety-like behavior, motor activity, memory impairment, motor coordination, GABA synthesis, GAD65, glutamatergic neurotransmission, GABAergic neurotransmission, serotonergic neurotransmission, norepinephrine, hippocampus, cerebellum, blood-brain barrier, neurotoxicity, bile acid homeostasis
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