The DOI matches its Crossref record; 51 of the 52 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
Flagged first, then by citations
1 of the 52 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 101–109 of 109
Association of Bile Acid with White Matter Hyperintensity in Cognitively Normal Older Adults
Xu, X. K., Zhang, Y., Lu, X. J., & Shi, B. (2023) · Indian Journal of Pharmaceutical Sciences · doi:10.36468/pharmaceutical-sciences.spl.698
Gut–brain communication through microbes
Green, M., & Foster, J. A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-90144-4.00002-1
Jakobsson, J. E., Carlsson, H., Erngren, I., Menezes, J., Krock, E., Hunt, M. A., Sohlin, J. T., Al-Grety, A., Sándor, K., Kosek, E., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.17.618791
The Gut Microbiota and NDG: What Is the Interplay
Haiba, S., Idriss, S., & Awad, M. (2024) · Springer eBooks · doi:10.1007/978-981-99-7557-0_30
Pocheron, A.-L. (2019) · theses.fr (ABES) · doi:10.70675/29969b86z2649z4b67zb315za23a1106f4ef
Rôle du récepteur Farnesoid X dans le contrôle central de l'homéostasie énergétique
Deckmyn, B. (2022) · theses.fr (ABES) · doi:10.70675/db76bb16z01f4z4f26zaf99za1003045be0c
Medina, C., Deme, P., Win, V., Nikitah, I., McKie, I., Song, M., Raudales, M., Regier, E., Amsden, E., Bendale, P., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.14.742173
The gut-liver-brain axis in alcohol use disorder: The emerging role of bile acid dysregulation
Lin, X., Yu, X., Bai, X., Isha, H. M., Wang, C., Zhang, R., & Yang, F. (2026) · Behavioural Brain Research · doi:10.1016/j.bbr.2026.116487 · Cited by 1
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
