Deletion of mouse FXR gene disturbs multiple neurotransmitter systems and alters neurobehavior
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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.
“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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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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Kim, I., Ahn, S.-H., Inagaki, T., Choi, M., Ito, S., Guo, G. L., Kliewer, S., & Gonzalez, F. (2007) · Journal of Lipid Research · doi:10.1194/jlr.m700330-jlr200 · Cited by 575 · see citing works
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 · see citing works
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 · see citing works
Seol, W., Choi, H.-S., & Moore, D. D. (1995) · Molecular Endocrinology · doi:10.1210/mend.9.1.7760852 · Cited by 389 · see citing works
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 381 · see citing works
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 · see citing works
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 328 · see citing works
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 · see citing works
Anxiety-Related Behaviors in Mice
Crawley, J. N., & Bailey, K. (2008) · Frontiers in neuroscience · doi:10.1201/noe1420052343.ch5 · Cited by 266 · see citing works
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 · see citing works
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 · see citing works
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 195 · see citing works
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 · see citing works
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 170 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 130 · see citing works
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 122 · see citing works
Eyles, D. W., Liu, P.-Y., Josh, P. F., & Cui, X. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.02.042 · Cited by 122 · see citing works
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 121 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 77 · see citing works
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 76 · see citing works
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 74 · see citing works
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 · see citing works
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 · see citing works
Akanuma, S., Hori, S., Ohtsuki, S., Fujiyoshi, M., & Terasaki, T. (2007) · Neurochemistry International · doi:10.1016/j.neuint.2007.08.012 · Cited by 47 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Anxiety-Related Behaviors in Mice -- Methods of Behavior Analysis in Neuroscience
Jj, B. (2009) · Cited by 15 · see citing works
[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 · see citing works
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 · see citing works
Flagged first, then by citations
1 of the 52 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis
Rusch, J. A., Layden, B. T., & Dugas, L. R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1130689 · Cited by 415 · see citing works
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 · see citing works
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 285 · see citing works
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 · see citing works
Bile acid signaling in neurodegenerative and neurological disorders
Grant, S. M., & DeMorrow, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21175982 · Cited by 185 · see citing works
Bile acids: a communication channel in the gut-brain axis
Monteiro-Cardoso, V. F., Corlianò, M., & Singaraja, R. R. (2021) · NeuroMolecular Medicine · doi:10.1007/s12017-020-08625-z · Cited by 145 · see citing works
Small talk: microbial metabolites involved in the signaling from microbiota to brain
Caspani, G., & Swann, J. R. (2019) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2019.08.001 · Cited by 138 · see citing works
Jena, P. K., Sheng, L., Di Lucente, J., Jin, L., Maezawa, I., & Wan, Y. Y. (2018) · The FASEB Journal · doi:10.1096/fj.201700984rr · Cited by 134 · see citing works
Bile Acids in Neurodegenerative Disorders
Ackerman, H. D., & Gerhard, G. S. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00263 · Cited by 120 · see citing works
Roles of bile acids signaling in neuromodulation under physiological and pathological conditions
Chen, X., Huang, X., Wang, D., Yu, D., Hou, S., Cui, H., & Song, L. (2023) · Cell & Bioscience · doi:10.1186/s13578-023-01053-z · Cited by 120 · see citing works
Huang, F., Pariante, C. M., & Borsini, A. (2022) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2021.09.021 · Cited by 117 · see citing works
Bile acids as key modulators of the brain-Gut-Microbiota axis in alzheimer’s disease
Mulak, A. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210608 · Cited by 114 · see citing works
McMillin, M., Frampton, G. A., Grant, S. M., Khan, S. H., Diocares, J., Petrescu, A. D., Wyatt, A., Kain, J., Jefferson, B., & DeMorrow, S. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00191 · Cited by 111 · see citing works
Identification of functional farnesoid X receptors in brain neurons
Huang, C., Wang, J., Hu, W., Wang, C., Lu, X., Tong, L., Wu, F., & Zhang, W. (2016) · FEBS Letters · doi:10.1002/1873-3468.12373 · Cited by 103 · see citing works
Xie, G., Wang, X., Jiang, R., Zhao, A., Yan, J., Zheng, X., Huang, F., Liu, X., Panee, J., Rajani, C., et al. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.10.030 · Cited by 84 · see citing works
Bile acids and neurological disease
Hurley, M. J., Bates, R., Macnaughtan, J., & Schapira, A. H. V. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108311 · Cited by 82 · see citing works
MahmoudianDehkordi, S., Bhattacharyya, S., Brydges, C. R., Jia, W., Fiehn, O., Rush, A. J., Dunlop, B. W., & Kaddurah-Daouk, R. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.937906 · Cited by 75 · see citing works
Bile acid receptors and signaling crosstalk in the liver, gut and brain
Ferrell, J. M., & Chiang, J. Y. L. (2021) · Liver Research · doi:10.1016/j.livres.2021.07.002 · Cited by 69 · see citing works
Celastrol Protects From Cholestatic Liver Injury Through Modulation of SIRT1-FXR Signaling
Zhao, Q., Liu, F., Cheng, Y., Xiao, X.-R., Hu, D., Tang, Y., Bao, W.-M., Yang, J., Jiang, T., Hu, J., et al. (2019) · Molecular & Cellular Proteomics · doi:10.1074/mcp.ra118.000817 · Cited by 68 · see citing works
Estrada, J. A., & Contreras, I. (2019) · Nutrients · doi:10.3390/nu11051076 · Cited by 65 · see citing works
Jena, P. K., Sheng, L., Nagar, N., Wu, C., Barile, D., Mills, D. A., & Wan, Y.-J. Y. (2018) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2018.04.007 · Cited by 60 · see citing works
The pathophysiological function of non-gastrointestinal farnesoid X receptor
Yan, N., Yan, T., Xia, Y., Hao, H., Wang, G., & Gonzalez, F. J. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107867 · Cited by 54 · see citing works
Potential gut–brain mechanisms behind adverse mental health outcomes of bariatric surgery
Brown, R. M., Guerrero-Hreins, E., Brown, W. A., le Roux, C. W., & Sumithran, P. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00520-2 · Cited by 49 · see citing works
Lee, B., Lee, S. M., Song, J. W., & Choi, J. W. (2024) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2024.009 · Cited by 48 · see citing works
Romero‐Ramírez, L., & Mey, J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25179279 · Cited by 49 · see citing works
Bile Acids in Hepatic Encephalopathy
DeMorrow, S. (2018) · Journal of Clinical and Experimental Hepatology · doi:10.1016/j.jceh.2018.04.011 · Cited by 47 · see citing works
Ma, C., Yuan, D., Renaud, S. J., Zhou, T., Yang, F., Liou, Y., Qiu, X., Zhou, L., & Guo, Y. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1040591 · Cited by 45 · see citing works
The clinical and mechanistic roles of bile acids in depression, Alzheimer's disease, and stroke
Wu, L., Zhao, M., Li, M., Guo, Q., Zhenxing, R., Xiaojiao, Z., & Chen, T. (2022) · PROTEOMICS · doi:10.1002/pmic.202100324 · Cited by 47 · see citing works
The Role of Bile Acids in the Human Body and in the Development of Diseases
Shulpekova, Y. O., Жаркова, М. С., Tkachenko, P. E., Тихонов, И. Н., Stepanov, A. A., Sinitsyna, A. A., Izotov, A., Butkova, T. V., Shulpekova, N. V., Лапина, Н. В., et al. (2022) · Molecules · doi:10.3390/molecules27113401 · Cited by 44 · see citing works
The Farnesoid X Receptor as a Master Regulator of Hepatotoxicity
Rausch, M., Samodelov, S. L., Visentin, M., & Kullak-Ublick, G. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232213967 · Cited by 40 · see citing works
Wu, M., Cheng, Y., Zhang, R., Han, W., Jiang, H., Bi, C., Zhang, Z., Ye, M., Lin, X., & Liu, Z. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117228 · Cited by 38 · see citing works
Chen, T., You, Y., Xie, G., Zheng, X., Zhao, A., Liu, J., Zhao, Q., Wang, S., Huang, F., Rajani, C., et al. (2018) · Analytical Chemistry · doi:10.1021/acs.analchem.7b02859 · Cited by 35 · see citing works
Metabolic Diffusion in Neuropathologies: The Relevance of Brain-Liver Axis
Vegas‐Suárez, S., Simón, J., Martínez‐Chantar, M. L., & Moratalla, R. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.864263 · Cited by 33 · see citing works
Stanimirov, B., Đanić, M., Pavlović, N., Zaklan, D., Lazarević, S., Mikov, M., & Stankov, K. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262412167 · Cited by 37 · see citing works
Paraiso, I. L., Tran, T. Q., Magaña, A. A., Kundu, P., Choi, J., Maier, C. S., Bobe, G., Raber, J., Kioussi, C., & Stevens, J. F. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.643857 · Cited by 31 · see citing works
Liver’s influence on the brain through the action of bile acids
Yeo, X. Y., Tan, L. Y., Chae, W. R., Lee, D., Lee, Y., Wüestefeld, T., & Jung, S. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1123967 · Cited by 33 · see citing works
Bile acids, bioactive signalling molecules in interoceptive gut‐to‐brain communication
Joyce, S. A., & O'Malley, D. (2022) · The Journal of Physiology · doi:10.1113/jp281727 · Cited by 31 · see citing works
A critical review of bile acids and their receptors in hepatic encephalopathy
Williams, E., Chu, C. S., & DeMorrow, S. (2021) · Analytical Biochemistry · doi:10.1016/j.ab.2021.114436 · Cited by 31 · see citing works
Sex Differences in Molecular Rhythms in the Human Cortex
Logan, R. W., Xue, X., Ketchesin, K. D., Hoffman, G. E., Roussos, P., Tseng, G. C., McClung, C. A., & Seney, M. L. (2021) · Biological Psychiatry · doi:10.1016/j.biopsych.2021.03.005 · Cited by 30 · see citing works
Depression-associated gut microbes, metabolites and clinical trials
Wang, M., Song, Z., Lai, S., Tang, F., Dou, L., & Yang, F. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1292004 · Cited by 29 · see citing works
Gut feelings: the microbiota-gut-brain axis on steroids
So, S. Y., & Savidge, T. (2021) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00294.2021 · Cited by 29 · see citing works
Fiaschini, N., Mancuso, M., Tanori, M., Colantoni, E., Vitali, R., Diretto, G., Lorenzo-Rebenaque, L., Stronati, L., & Negroni, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232214254 · Cited by 27 · see citing works
Bosma, P. J., Wits, M., & Elferink, R. P. J. O. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010273 · Cited by 26 · see citing works
Evidence and Mechanism of Bile Acid–Mediated Gut-Brain Axis in Anxiety and Depression
Idahosa, S. O., Diarra, R., Ranu, H. K., Nasiri, R. H., & Higuchi, S. (2024) · American Journal Of Pathology · doi:10.1016/j.ajpath.2024.10.019 · Cited by 25 · see citing works
Kraus, K., KLEENE, R. B., Henis, M., Braren, I., Kataria, H., Sharaf, A. L., Loers, G., Schachner, M., & Lutz, D. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-0901-7 · Cited by 24 · see citing works
A combination of three plasma bile acids as a putative biomarker for schizophrenia
Tao, Y., Zheng, F., Cui, D., Huang, F., & Wu, X. (2020) · Acta Neuropsychiatrica · doi:10.1017/neu.2020.42 · Cited by 23 · see citing works
Boonyarattanasoonthorn, T., Kongratanapasert, T., Maiuthed, A., Hamlin, R. L., Kijtawornrat, A., & Khemawoot, P. (2022) · Scientific Reports · doi:10.1038/s41598-022-24935-7 · Cited by 22 · see citing works
The role of the gut microbiome in disorders of gut–brain interaction
Gawey, B. J., Mars, R. A. T., & Kashyap, P. (2024) · FEBS Journal · doi:10.1111/febs.17200 · Cited by 28 · see citing works
Research Progress on the Mechanism of Bile Acids and Their Receptors in Depression
Zhao, X.-Y., Zheng, I., Huang, W.-J., Tang, D., Zhao, M.-D., Hou, R., Huang, Y., Shi, Y.-X., Zhu, W., & Wang, S.-J. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26094023 · Cited by 27 · see citing works
Wang, B., Han, D. W., Hu, X., Chen, J., Liu, Y., & Wu, J. (2024) · Microbiological Research · doi:10.1016/j.micres.2024.127865 · Cited by 22 · see citing works
Darmanto, A. G., Yen, T., Jan, J., Linh, T. T. D., Taliyan, R., Yang, C. H., & Sheu, J. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107564 · Cited by 21 · see citing works
Deckmyn, B., Domenger, D., Blondel, C., Ducastel, S., Nicolas, E., Dorchies, E., Caron, É., Charton, J., Vallez, E., Deprez, B. P., et al. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.808603 · Cited by 23 · see citing works
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 · see citing works
On the Evolution of Bile Salts and the Farnesoid X Receptor in Vertebrates
Frisch, K., & Alstrup, A. K. O. (2017) · Physiological and Biochemical Zoology · doi:10.1086/695810 · Cited by 19 · see citing works
Farnesoid X receptor: a potential therapeutic target in multiple organs.
Zhang, C., Wang, Z., Feng, Q., Chen, W.-D., & Wang, Y.-D. (2021) · Histology and Histopathology · doi:10.14670/hh-18-301 · Cited by 16 · see citing works
Lack of CAR impacts neuronal function and cerebrovascular integrity in vivo
Boussadia, B., Gangarossa, G., Mselli-Lakhal, L., Rousset, M.-C., de Bock, F., Lassere, F., Ghosh, C., Pascussi, J., Janigro, D., & Marchi, N. (2016) · Experimental Neurology · doi:10.1016/j.expneurol.2016.05.018 · Cited by 17 · see citing works
Czarnecka, A. M., Milewski, K., Albrecht, J., & Zielińska, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207750 · Cited by 16 · see citing works
Underneath the Gut–Brain Axis in IBD—Evidence of the Non-Obvious
Boldyreva, L. V., Evtushenko, A. A., Lvova, M. N., Morozova, K. N., & Владимировна, К. Е. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252212125 · Cited by 16 · see citing works
Portlock, T., Shama, T., Kakon, S. H., Hartjen, B., Pook, C. J., Wilson, B. C., Bhuttor, A., Ho, D., Shennon, I., Engelstad, A., et al. (2025) · Nature Communications · doi:10.1038/s41467-024-55798-3 · Cited by 16 · see citing works
Serotonin/5-HT1A Signaling in the Neurovascular Unit Regulates Endothelial CLDN5 Expression
Sugimoto, K., Ichikawa‐Tomikawa, N., Nishiura, K., Kunii, Y., Sano, Y., Shimizu, F., Kakita, A., Kanda, T., Imura, T., & Chiba, H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010254 · Cited by 16 · see citing works
Qing'E formula alleviates the aging process in D-galactose-induced aging mice
Zhong, L., Huang, F., Shi, H., Wu, H., Zhang, B., Wu, X., Wei, X., & Wang, Z. (2016) · Biomedical Reports · doi:10.3892/br.2016.667 · Cited by 16 · see citing works
Li, J., Liu, H., Hu, X., Zhang, S., Yu, Q., Kuang, G., Liu, L., Yu, D., Huang, J., Xia, Y. F., et al. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113087 · Cited by 14 · see citing works
Baldi, S., Turrini, M., Cei, F., Menicatti, M., Bartolucci, G., & Amedei, A. (2026) · BioFactors · doi:10.1002/biof.70078 · Cited by 13 · see citing works
The contributions of bacteria metabolites to the development of hepatic encephalopathy
Gilbert, M. C., Setayesh, T., & Wan, Y. Y. (2022) · Liver Research · doi:10.1016/j.livres.2022.11.005 · Cited by 11 · see citing works
Bile acid interactions with neurotransmitter transporters
Romanazzi, T., Zanella, D., Bhatt, M., Iacovo, A. D., Galli, A., & Bossi, E. (2023) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1161930 · Cited by 11 · see citing works
Wang, X., Xie, J., Ma, H., Li, G., Li, M., Li, S., Sun, X., Zhao, Y., Sun, W., Yang, S., et al. (2023) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2023.2271965 · Cited by 11 · see citing works
The bile acid chenodeoxycholic acid associates with reduced stroke in humans and mice
Monteiro-Cardoso, V. F., Yeo, X. Y., Bae, H., Mayan, D. C., Wehbe, M., Lee, S., Krishna-K, K., Baek, S. H., Palomera, L. F., Wu, L. H., et al. (2024) · Journal of Lipid Research · doi:10.1016/j.jlr.2024.100712 · Cited by 11 · see citing works
Wang, J., Han, S., Luo, Y., Zhang, J., Wang, Y., & Chen, L. (2024) · Aquaculture · doi:10.1016/j.aquaculture.2024.742033 · Cited by 10 · see citing works
Rosell-Cardona, C., Cryan, J., Clarke, G., & Kittel-Schneider, S. (2025) · npj Biofilms and Microbiomes · doi:10.1038/s41522-025-00749-z · Cited by 10 · see citing works
Mechanisms of the effect of gut microbes on depression through the microbiota-gut-brain axis
Zhou, X., Wang, S., Wang, X., Chen, X., Zhou, P., Ma, K., & Zhang, P. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1634548 · Cited by 13 · see citing works
Bile Acids Gate Dopamine Transporter Mediated Currents
Romanazzi, T., Zanella, D., Cheng, M. H., Smith, B., Carter, A. M., Galli, A., Bahar, İ., & Bossi, E. (2021) · Frontiers in Chemistry · doi:10.3389/fchem.2021.753990 · Cited by 10 · see citing works
Gut microbiome metabolites as key actors in atherosclerosis co-depression disease
Liao, X.-X., Wu, X., Zhou, Y.-L., Li, J., Wen, Y.-L., & Zhou, J. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.988643 · Cited by 9 · see citing works
Zhang, Y., Li, J., Li, J., Wang, Y., Cui, M., Li, W., Chen, X., & Jiang, Y. (2025) · GeroScience · doi:10.1007/s11357-025-01790-8 · Cited by 9 · see citing works
Wang, H., Nie, Y., Luo, Y., Sun, Z., He, Y., & Yang, J. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.157394 · Cited by 9 · see citing works
Integrated metabolomics and network pharmacology to reveal the mechanism of areca nut addiction
Li, M., Pang, X., Guo, Z., Yang, Y., Gu, Z., & Zhang, L. (2023) · Addiction Biology · doi:10.1111/adb.13352 · Cited by 9 · see citing works
Wang, Y., & Zhang, Y. (2025) · Neuropharmacology and Therapy · doi:10.15212/npt-2025-0008 · Cited by 8 · see citing works
Wang, J., Zhang, Y., Wu, Q., Zhong, Y., Xu, Z., & Yang, J. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1757551 · Cited by 9 · see citing works
Cai, W., Li, C., Su, Z., Cao, J., Chen, Z., Chen, Y., Guo, Z., Cai, J., & Xu, F. (2023) · PeerJ · doi:10.7717/peerj.16407 · Cited by 7 · see citing works
Peyer’s Patch: Possible target for modulating the Gut-Brain-Axis through microbiota
Asgari, R., Bazzazan, M. A., Jirandehi, A. K., Yousefzadeh, S., Alaei, M., & Shahbaz, S. K. (2024) · Cellular Immunology · doi:10.1016/j.cellimm.2024.104844 · Cited by 5 · see citing works
Reuter, M. A., Moreno, R., Tucker, M., Shishani, R., Bustamante, J. M., Marfori, Z., Richieri, T., Valenzuela, A. E., Taha, A. Y., Lein, P. J., et al. (2025) · Comprehensive physiology · doi:10.1002/cph4.70034 · Cited by 4 · see citing works
Tao, Y., Li, Z., Yuan, J., Wu, H., Shi, H., Wu, X., & Huang, F. (2024) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2024.100856 · Cited by 4 · see citing works
Fan, X., Dong, W., Huang, Y., Shu, Y., Yan, Y., Mi, J., Lu, L., Zeng, X., & Cao, Y. (2024) · Foods · doi:10.3390/foods13233812 · Cited by 4 · see citing works
Ye, W., Bai, X., Zhao, Y., Du, Z., Liu, F., Wang, Y., & Chen, W. (2025) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2025.167750 · Cited by 4 · see citing works
Metabolites from the Gut Microbiota and the Role in the Gut-Brain Axis
Fukushima, K. (2022) · Science Insights · doi:10.15354/si.22.re037 · Cited by 4 · see citing works
MahmoudianDehkordi, S., Bhattacharyya, S., Brydges, C. R., Jia, W. P., Fiehn, O., Rush, A. J., Dunlop, B. W., & Kaddurah-Daouk, R. F. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.04.04.485514 · Cited by 4 · see citing works
Hung, Y.-A., Kuo, T.-C., Tseng, Y. J., Shang, C., & Gau, S. S. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03393-5 · Cited by 3 · see citing works
Post-bariatric surgery quality-of-life decline: analysis of the gut–brain axis
Jiao, Y., Zhu, S., Xue, H., Wang, Y., Wang, Y., & Hou, D. (2025) · Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity · doi:10.1007/s40519-025-01784-7 · Cited by 3 · see citing works
Unveiling the rumen-microbiome-brain circuit: a unique dimension of gut-brain axis in ruminants
Joshi, H., Bernard, B., Lemley, C. O., Wang, Z., & Fan, P. F. (2025) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-025-01289-4 · Cited by 4 · see citing works
Metabolomics and the Gut–Brain Axis
Caspani, G., Harvey, M., & Swann, J. R. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-99971-7.00003-5 · Cited by 3 · see citing works
Chen, L., Li, W., Mo, D., Meng, X., Yao, L., Zhang, X., & Liu, H. (2025) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s523570 · Cited by 2 · see citing works
Bile Acids and Their Value for Central Nervous System
Shulpekova, Y. O., Tkachenko, P. E., Shirokova, E. N., & Damulin, I. V. (2022) · Russian Journal of Gastroenterology Hepatology Coloproctology · doi:10.22416/1382-4376-2021-31-5-7-15 · Cited by 2 · see citing works
Aldicarb disturbed bile acid, steroid hormone and oxylipin homeostasis in C57BL/6 J mice
Liu, X., Tu, P., Zhang, Y., Xu, W., Shan, J., & Gao, B. (2024) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2024.116285 · Cited by 1 · see citing works
Wang, Z., Zhou, M., Dang, Y., Huang, X., Xu, C., Xu, F., Xu, X., Li, P., Zhang, S., Shi, H., et al. (2025) · PLoS ONE · doi:10.1371/journal.pone.0337941 · Cited by 1 · see citing works
The bridging role of gut microbiota-derived metabolites in neuropathic pain comorbid with anxiety
Bian, J., & 白金柱 (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1752839 · Cited by 1 · see citing works
Banerjee, S., Panjwani, D., Singh, S., & Singh, T. G. (2026) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2026.578942 · Cited by 1 · see citing works
Neurologic Consequences of Liver Disease
McMillin, M., Rhodes, K., & DeMorrow, S. (2026) · American Journal Of Pathology · doi:10.1016/j.ajpath.2026.07.014 · Cited by 1 · see citing works
The Gut Microbiota and NDG: What Is the Interplay
Haiba, S., Idriss, S., & Awad, M. (2024) · Springer eBooks · doi:10.1007/978-981-19-3949-5_30-1 · Cited by 1 · see citing works
Zhou, J., Tao, Y., Zhu, H., Wu, H., Shi, H., Huang, F., & Wu, X. (2020) · Neuroreport · doi:10.1097/wnr.0000000000001437 · Cited by 1 · see citing works
Celastrol通过调制SIRT1-FXR信号传导来保护胆汁淤积肝损伤* [S]
齐泽, 方刘, 闫成, 薛荣萧, 丹胡, 丹., 莹梅唐, 魏民宝, 金辉杨, 陶江, 贾鹏胡, et al. (2019)
Monteiro-Cardoso, V. F., Yeo, X. Y., Bae, H., Mayan, D. C., Wehbe, M., Lee, S., Krishna-K, K., Baek, S. H., Palomera, L. F., Shanmugam, S., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.12.11.520005
- 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 · 2014: 1
- 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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