{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T01:52:22Z","timestamp":1788054742157,"version":"build-2784847793"},"reference-count":71,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation (DFG)","doi-asserted-by":"publisher","award":["457840828"],"award-info":[{"award-number":["457840828"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is the most common chronic liver disease in Western countries. It is becoming increasingly evident that peripheral organ-centered inflammatory diseases, including liver diseases, are linked with brain dysfunctions. Therefore, this study aims to unravel the effect of MASLD on brain histology, cognitive functions, and neurotransmitters. For this purpose, mice fed for 48 weeks on standard (SD) or Western diet (WD) were evaluated by behavioral tests, followed by sacrifice and analysis of the liver-brain axis including histopathology, immunohistochemistry, and biochemical analyses. Histological analysis of the liver showed features of Metabolic Dysfunction-Associated Steatohepatitis (MASH) in the WD-fed mice including lipid droplet accumulation, inflammation, and fibrosis. This was accompanied by an elevation of transaminase and alkaline phosphatase activities, increase in inflammatory cytokine and bile acid concentrations, as well as altered amino acid concentrations in the blood. Interestingly, compromised blood capillary morphology coupled with astrogliosis and microgliosis were observed in brain hippocampus of the WD mice, indicating neuroinflammation or a disrupted neurovascular unit. Moreover, attention was impaired in WD-fed mice along with the observations of impaired motor activity and balance, enhanced anxiety, and stereotyped head-twitch response (HTR) behaviors. Analysis of neurotransmitters and modulators including dopamine, serotonin, GABA, glutamate, and acetylcholine showed region-specific dysregulation in the brain of the WD-fed mice. In conclusion, the induction of MASH in mice is accompanied by the alteration of cellular morphology and neurotransmitter expression in the brain, associated with compromised cognitive functions.<\/jats:p>","DOI":"10.3390\/cells12182331","type":"journal-article","created":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T21:08:36Z","timestamp":1695330516000},"page":"2331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Cognitive Functions, Neurotransmitter Alterations, and Hippocampal Microstructural Changes in Mice Caused by Feeding on Western Diet"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4318-3375","authenticated-orcid":false,"given":"Raly James Perez","family":"Custodio","sequence":"first","affiliation":[{"name":"Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), Ardeystrasse 67, 44139 Dortmund, 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Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, South Valley University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), Ardeystrasse 67, 44139 Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1025-7849","authenticated-orcid":false,"given":"J\u00f6rg","family":"Reinders","sequence":"additional","affiliation":[{"name":"Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), Ardeystrasse 67, 44139 Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4018-2406","authenticated-orcid":false,"given":"Julia","family":"Bornhorst","sequence":"additional","affiliation":[{"name":"Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Gau\u00dfstra\u00dfe 20, 42119 Wuppertal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1650-7899","authenticated-orcid":false,"given":"Ann-Kathrin","family":"Weishaupt","sequence":"additional","affiliation":[{"name":"Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Gau\u00dfstra\u00dfe 20, 42119 Wuppertal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdel-latif","family":"Seddek","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, South Valley University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahany","family":"Abbas","sequence":"additional","affiliation":[{"name":"Histology Department, Faculty of Medicine, South Valley University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Friebel","sequence":"additional","affiliation":[{"name":"Institute of Computer Science & Saxonian Incubator for Clinical Research (SIKT), University of Leipzig, Haertelstra\u00dfe 16-18, 04107 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Hoehme","sequence":"additional","affiliation":[{"name":"Institute of Computer Science & Saxonian Incubator for Clinical Research (SIKT), University of Leipzig, Haertelstra\u00dfe 16-18, 04107 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6382-0183","authenticated-orcid":false,"given":"Stephan","family":"Getzmann","sequence":"additional","affiliation":[{"name":"Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), Ardeystrasse 67, 44139 Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan G.","family":"Hengstler","sequence":"additional","affiliation":[{"name":"Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), Ardeystrasse 67, 44139 Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3215-9262","authenticated-orcid":false,"given":"Christoph","family":"van Thriel","sequence":"additional","affiliation":[{"name":"Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), Ardeystrasse 67, 44139 Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0695-3403","authenticated-orcid":false,"given":"Ahmed","family":"Ghallab","sequence":"additional","affiliation":[{"name":"Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), Ardeystrasse 67, 44139 Dortmund, 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(2021). Spatio-Temporal Multiscale Analysis of Western Diet-Fed Mice Reveals a Translationally Relevant Sequence of Events during NAFLD Progression. Cells, 10.","DOI":"10.3390\/cells10102516"},{"key":"ref_3","first-page":"984","article-title":"Obesity and Cardiovascular Disease: A Scientific Statement from the American Heart Association","volume":"143","author":"Poirier","year":"2021","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1002\/pd.4932","article-title":"Maternal Obesity and Neurodevelopmental and Psychiatric Disorders in Offspring","volume":"37","author":"Edlow","year":"2017","journal-title":"Prenat. Diagn."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.tem.2021.10.005","article-title":"The Menace of Obesity to Depression and Anxiety Prevalence","volume":"33","author":"Fulton","year":"2022","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1542\/peds.2010-2742","article-title":"Risk-Taking Behaviors of Adolescents with Extreme Obesity: Normative or Not?","volume":"127","author":"Ratcliff","year":"2011","journal-title":"Pediatrics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.4254\/wjh.v12.i12.1168","article-title":"Metabolic Associated Fatty Liver Disease: Addressing a New Era in Liver Transplantation","volume":"12","author":"Gill","year":"2020","journal-title":"World J. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.jhep.2018.05.036","article-title":"Modeling NAFLD Disease Burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the Period 2016\u20132030","volume":"69","author":"Estes","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jhep.2019.08.027","article-title":"A Cross-Sectional Study of the Public Health Response to Non-Alcoholic Fatty Liver Disease in Europe","volume":"72","author":"Lazarus","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Soto-Angona, \u00d3., Anmella, G., Vald\u00e9s-Florido, M.J., De Uribe-Viloria, N., Carvalho, A.F., Penninx, B.W.J.H., and Berk, M. (2020). Non-Alcoholic Fatty Liver Disease (NAFLD) as a Neglected Metabolic Companion of Psychiatric Disorders: Common Pathways and Future Approaches. BMC Med., 18.","DOI":"10.1186\/s12916-020-01713-8"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/hep.24418","article-title":"Obesity Is an Independent Risk Factor for Clinical Decompensation in Patients with Cirrhosis","volume":"54","author":"Berzigotti","year":"2011","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1056\/NEJMoa2029349","article-title":"Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease","volume":"385","author":"Sanyal","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1111\/ejn.16070","article-title":"Age and an Obesogenic Diet Affect Mouse Behaviour in a Sex-Dependent Manner","volume":"58","author":"Mort","year":"2023","journal-title":"Eur. J. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.jhep.2015.11.018","article-title":"Model-Guided Identification of a Therapeutic Strategy to Reduce Hyperammonemia in Liver Diseases","volume":"64","author":"Ghallab","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6224","DOI":"10.1038\/s41598-017-04574-z","article-title":"Physiologically-Based Modelling in Mice Suggests an Aggravated Loss of Clearance Capacity after Toxic Liver Damage","volume":"7","author":"Schenk","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3349","DOI":"10.1007\/s00204-022-03395-y","article-title":"Inhibition of Cytochrome P450 Enhances the Nephro- and Hepatotoxicity of Ochratoxin A","volume":"96","author":"Hassan","year":"2022","journal-title":"Arch. Toxicol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/hep4.1797","article-title":"Transcriptomic Cross-Species Analysis of Chronic Liver Disease Reveals Consistent Regulation Between Humans and Mice","volume":"6","author":"Holland","year":"2022","journal-title":"Hepatol. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1007\/s00204-022-03361-8","article-title":"Hypoalbuminemia Affects the Spatio-Temporal Tissue Distribution of Ochratoxin A in Liver and Kidneys: Consequences for Organ Toxicity","volume":"96","author":"Hassan","year":"2022","journal-title":"Arch. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1021\/acs.jproteome.9b00640","article-title":"Skyline for Small Molecules: A Unifying Software Package for Quantitative Metabolomics HHS Public Access","volume":"19","author":"Adams","year":"2020","journal-title":"J. Proteome Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jhep.2022.01.020","article-title":"Interruption of Bile Acid Uptake by Hepatocytes after Acetaminophen Overdose Ameliorates Hepatotoxicity","volume":"77","author":"Ghallab","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"109526","DOI":"10.1016\/j.celrep.2021.109526","article-title":"Epigenomic and Transcriptional Profiling Identifies Impaired Glyoxylate Detoxification in NAFLD as a Risk Factor for Hyperoxaluria","volume":"36","author":"Gianmoena","year":"2021","journal-title":"Cell Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ghallab, A., Myllys, M., Holland, C.H., Zaza, A., Murad, W., Hassan, R., Ahmed, Y.A., Abbas, T., Abdelrahim, E.A., and Schneider, K.M. (2019). Influence of Liver Fibrosis on Lobular Zonation. Cells, 8.","DOI":"10.3390\/cells8121556"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Weishaupt, A.K., Kubens, L., Ruecker, L., Schwerdtle, T., Aschner, M., and Bornhorst, J. (2023). A Reliable Method Based on Liquid Chromatography\u2013Tandem Mass Spectrometry for the Simultaneous Quantification of Neurotransmitters in Caenorhabditis elegans. Molecules, 28.","DOI":"10.3390\/molecules28145373"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.neuroscience.2018.08.008","article-title":"Overexpression of the Thyroid Hormone-Responsive (THRSP) Gene in the Striatum Leads to the Development of Inattentive-like Phenotype in Mice","volume":"390","author":"Custodio","year":"2018","journal-title":"Neuroscience"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.pnpbp.2018.08.012","article-title":"The Atxn7-Overexpressing Mice Showed Hyperactivity and Impulsivity Which Were Ameliorated by Atomoxetine Treatment: A Possible Animal Model of the Hyperactive-Impulsive Phenotype of ADHD","volume":"88","author":"Botanas","year":"2019","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"108619","DOI":"10.1016\/j.neuropharm.2021.108619","article-title":"R (\u2212)-Methoxetamine Exerts Rapid and Sustained Antidepressant Effects and Fewer Behavioral Side Effects Relative to S (+)-Methoxetamine","volume":"193","author":"Botanas","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1135929","DOI":"10.3389\/fphar.2023.1135929","article-title":"Deletion of Cryab Increases the Vulnerability of Mice to the Addiction-like Effects of the Cannabinoid JWH-018 via Upregulation of Striatal NF-\u039aB Expression","volume":"14","author":"Sayson","year":"2023","journal-title":"Front. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Custodio, R.J.P., Sayson, L.V., Botanas, C.J., Abiero, A., You, K.Y., Kim, M., Lee, H.J., Yoo, S.Y., Lee, K.W., and Lee, Y.S. (2020). 25B-NBOMe, a Novel N-2-Methoxybenzyl-Phenethylamine (NBOMe) Derivative, May Induce Rewarding and Reinforcing Effects via a Dopaminergic Mechanism: Evidence of Abuse Potential. Addict. Biol., 25.","DOI":"10.1111\/adb.12850"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3197","DOI":"10.1038\/s41598-020-59921-4","article-title":"Maturational Delay and Asymmetric Information Flow of Brain Connectivity in SHR Model of ADHD Revealed by Topological Analysis of Metabolic Networks","volume":"10","author":"Ha","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Custodio, R.J.P., Kim, M., Sayson, L.V., Lee, H.J., Ortiz, D.M., Kim, B.-N., Kim, H.J., and Cheong, J.H. (2021). Low Striatal T3 Is Implicated in Inattention and Memory Impairment in an ADHD Mouse Model Overexpressing Thyroid Hormone-Responsive Protein. Commun. Biol., 4.","DOI":"10.1038\/s42003-021-02633-w"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Custodio, R.J.P., Kim, H.J., Kim, J., Ortiz, D.M., Kim, M., Buctot, D., Sayson, L.V., Lee, H.J., Kim, B.-N., and Yi, E.C. (2023). Hippocampal Dentate Gyri Proteomics Reveals Wnt Signaling Involvement in the Behavioral Impairment in the THRSP-Overexpressing ADHD Mouse Model. Commun. Biol., 6.","DOI":"10.1038\/s42003-022-04387-5"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"761456","DOI":"10.3389\/fnins.2021.761456","article-title":"Gut Microbiome, Inflammation, and Cerebrovascular Function: Link Between Obesity and Cognition","volume":"15","author":"Olsthoorn","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1111\/j.1467-789X.2011.00920.x","article-title":"A Review of the Association between Obesity and Cognitive Function across the Lifespan: Implications for Novel Approaches to Prevention and Treatment","volume":"12","author":"Smith","year":"2011","journal-title":"Obes. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.cytogfr.2016.02.003","article-title":"The Light and the Dark Sides of Interleukin-10 in Immune-Mediated Diseases and Cancer","volume":"30","author":"Geginat","year":"2016","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kany, S., Vollrath, J.T., and Relja, B. (2019). Cytokines in Inflammatory Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20236008"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"797862","DOI":"10.1155\/2015\/797862","article-title":"Elevated Blood Ammonia Level Is a Potential Biological Risk Factor of Behavioral Disorders in Prisoners","volume":"2015","author":"Duan","year":"2015","journal-title":"Behav. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5521","DOI":"10.1073\/pnas.1423968112","article-title":"Hyperammonemia in Gene-Targeted Mice Lacking Functional Hepatic Glutamine Synthetase","volume":"112","author":"Qvartskhava","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"17558","DOI":"10.1038\/s41598-022-22423-6","article-title":"A Mouse Model of Hepatic Encephalopathy: Bile Duct Ligation Induces Brain Ammonia Overload, Glial Cell Activation and Neuroinflammation","volume":"12","author":"Claeys","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.mayocp.2015.03.003","article-title":"Refining the Ammonia Hypothesis: A Physiology-Driven Approach to the Treatment of Hepatic Encephalopathy","volume":"90","author":"Tapper","year":"2015","journal-title":"Mayo Clin. Proc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.ebiom.2018.10.030","article-title":"Dysregulated Bile Acid Signaling Contributes to the Neurological Impairment in Murine Models of Acute and Chronic Liver Failure","volume":"37","author":"Xie","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1136\/jnnp.63.3.279","article-title":"Neurology and the Liver","volume":"63","author":"Jones","year":"1997","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/cld.1211","article-title":"Behavioral Health Disorders Related to Nonalcoholic Steatohepatitis","volume":"20","author":"Sharma","year":"2022","journal-title":"Clin. Liver Dis."},{"key":"ref_43","first-page":"83","article-title":"Brain and the Liver: Cerebral Edema, Hepatic Encephalopathy and Beyond","volume":"7","author":"Kumar","year":"2017","journal-title":"Hepatic Crit. Care"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Knight, P., Chellian, R., Wilson, R., Behnood-Rod, A., Panunzio, S., and Bruijnzeel, A.W. (2021). Sex Differences in the Elevated Plus-Maze Test and Large Open Field Test in Adult Wistar Rats. Pharmacol. Biochem. Behav., 204.","DOI":"10.1016\/j.pbb.2021.173168"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e14522","DOI":"10.1016\/j.heliyon.2023.e14522","article-title":"Comparative Analysis between Open Field and Elevated Plus Maze Tests as a Method for Evaluating Anxiety-like Behavior in Mice","volume":"9","author":"Castro","year":"2023","journal-title":"Heliyon"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.bbr.2008.10.007","article-title":"Do Rats Really Express Neophobia towards Novel Objects? Experimental Evidence from Exposure to Novelty and to an Object Recognition Task in an Open Space and an Enclosed Space","volume":"197","author":"Ennaceur","year":"2009","journal-title":"Behav. Brain Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.bbadis.2015.10.004","article-title":"Glial Influences on BBB Functions and Molecular Players in Immune Cell Trafficking","volume":"1862","author":"Kebir","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.3389\/fimmu.2020.01818","article-title":"Affective Immunology: The Crosstalk Between Microglia and Astrocytes Plays Key Role?","volume":"11","author":"Yang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"21568","DOI":"10.1038\/srep21568","article-title":"Chronic Consumption of a Western Diet Induces Robust Glial Activation in Aging Mice and in a Mouse Model of Alzheimer\u2019s Disease","volume":"6","author":"Graham","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"985","DOI":"10.3389\/fnins.2018.00985","article-title":"Neurochemical Modifications in the Hippocampus, Cortex and Hypothalamus of Mice Exposed to Long-Term High-Fat Diet","volume":"12","author":"Lizarbe","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"23133","DOI":"10.18632\/aging.203607","article-title":"Short-Term High-Fat Diet Favors the Appearances of Apoptosis and Gliosis by Activation of ERK1\/2\/P38MAPK Pathways in Brain","volume":"13","author":"Xu","year":"2021","journal-title":"Aging"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s10571-018-0632-3","article-title":"Dopamine: Functions, Signaling, and Association with Neurological Diseases","volume":"39","author":"Klein","year":"2019","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1002960","DOI":"10.3389\/fnsyn.2022.1002960","article-title":"Segregation of D1 and D2 Dopamine Receptors in the Striatal Direct and Indirect Pathways: An Historical Perspective","volume":"14","author":"Gerfen","year":"2023","journal-title":"Front. Synaptic Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"14835","DOI":"10.1073\/pnas.1616515114","article-title":"Dopamine Release from the Locus Coeruleus to the Dorsal Hippocampus Promotes Spatial Learning and Memory","volume":"113","author":"Kempadoo","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Colognesi, M., Gabbia, D., and De Martin, S. (2020). Depression and Cognitive Impairment-Extrahepatic Manifestations of NAFLD and NASH. Biomedicines, 8.","DOI":"10.3390\/biomedicines8070229"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1007\/s11011-014-9630-4","article-title":"Low-Grade Chronic Inflammation Induces Behavioral Stereotypy in Rats","volume":"30","author":"Akseki","year":"2015","journal-title":"Metab Brain Dis."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Higarza, S.G., Arboleya, S., Gueimonde, M., G\u00f3mez-L\u00e1zaro, E., Arias, J.L., and Arias, N. (2019). Neurobehavioral Dysfunction in Non-Alcoholic Steatohepatitis Is Associated with Hyperammonemia, Gut Dysbiosis, and Metabolic and Functional Brain Regional Deficits. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0223019"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Radford-Smith, D.E., Patel, P.J., Irvine, K.M., Russell, A., Siskind, D., Anthony, D.C., Powell, E.E., and Probert, F. (2022). Depressive Symptoms in Non-Alcoholic Fatty Liver Disease Are Identified by Perturbed Lipid and Lipoprotein Metabolism. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0261555"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/j.1476-5381.1963.tb01302.x","article-title":"A Method for Assessing the Effects of Drugs on the Central Actions of 5-Hydroxytryptamine","volume":"20","author":"Corne","year":"1963","journal-title":"Br. J. Pharmacol. Chemother."},{"key":"ref_60","first-page":"699","article-title":"Direct Injection of 5-HT2A Receptor Agonists into the Medial Prefrontal Cortex Produces a Head-Twitch Response in Rats","volume":"282","author":"Willins","year":"1997","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1111\/ene.14486","article-title":"Acquired Hepatocerebral Degeneration and Hepatic Encephalopathy: One or Two Entities?","volume":"27","author":"Malaquias","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref_62","first-page":"1","article-title":"Uncommon Movement Disorders in Chronic Hepatic Disease with Response to Rifaximin","volume":"9","author":"Sousa","year":"2019","journal-title":"Tremor Other Hyperkinetic Mov."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1080\/00365521.2021.1919198","article-title":"Propranolol-Induced Hallucinations Mimicking Encephalopathy in a Patient with Liver Cirrhosis","volume":"56","author":"Molinaro","year":"2021","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s00213-013-3006-z","article-title":"Characterization of the Head-Twitch Response Induced by Hallucinogens in Mice: Detection of the Behavior Based on the Dynamics of Head Movement","volume":"227","author":"Halberstadt","year":"2013","journal-title":"Psychopharmacology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1007\/s00213-022-06106-8","article-title":"How to Account for Hallucinations in the Interpretation of the Antidepressant Effects of Psychedelics: A Translational Framework","volume":"239","author":"Magaraggia","year":"2022","journal-title":"Psychopharmacology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1007\/s00702-014-1180-8","article-title":"Glutamate as a Neurotransmitter in the Healthy Brain","volume":"121","author":"Zhou","year":"2014","journal-title":"J. Neural Transm."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Czapski, G.A., and Strosznajder, J.B. (2021). Glutamate and GABA in Microglia-Neuron Cross-Talk in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111677"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/S0149-7634(96)00034-6","article-title":"Glutamatergic Control over Brain Dopamine Release In Vivo and In Vitro","volume":"21","author":"Whitton","year":"1997","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.jhep.2006.06.019","article-title":"Hypolocomotion in Rats with Chronic Liver Failure Is due to Increased Glutamate and Activation of Metabotropic Glutamate Receptors in Substantia Nigra","volume":"45","author":"Cauli","year":"2006","journal-title":"J. Hepatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s12974-016-0549-z","article-title":"Neuroinflammation Increases GABAergic Tone and Impairs Cognitive and Motor Function in Hyperammonemia by Increasing GAT-3 Membrane Expression. Reversal by Sulforaphane by Promoting M2 Polarization of Microglia","volume":"13","author":"Agusti","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3525","DOI":"10.1523\/JNEUROSCI.4390-14.2015","article-title":"Dopamine Directly Modulates GABAA Receptors","volume":"35","author":"Hoerbelt","year":"2015","journal-title":"J. Neurosci."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/18\/2331\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:55:17Z","timestamp":1760129717000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/18\/2331"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,21]]},"references-count":71,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["cells12182331"],"URL":"https:\/\/doi.org\/10.3390\/cells12182331","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,21]]}}}