{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:25:02Z","timestamp":1790130302607,"version":"4.0.1"},"reference-count":102,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Medicine and Pharmacy of Craiova, Romania"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) has been associated with depression and inadequate response to antidepressants. While ketamine has demonstrated efficacy in treating depression, its impact on pre-existing liver injury and depression remains unclear. This study aimed to evaluate the effects of ketamine treatment in a murine model of depression and liver damage, considering age-related differences. Young and aged male C57BL\/6N mice were submitted to chronic unpredictable mild stress (CUMS) and methionine\u2013choline-deficient (MCD) diet to induce depressive-like behavior and NAFLD. Behavioral testing (sucrose preference test, open field test, novel object recognition test, Crawley\u2019s sociability test) were used to assess ketamine\u2019s (50 mg\/kg) effect on behavior. Hepatic ultrasonography was utilized to evaluate liver status. The cortical and hippocampal NeuN+, GFAP+, and Iba1+ signals were quantified for each animal. Ketamine administration proved effective in relieving anhedonia and anxiety-like behavior, regardless of liver damage. Although ketamine treatment did not improve memory in animals with liver damage, it enhanced sociability, particularly in aged subjects. The acute administration of ketamine did not affect the severity of liver injury, but seems to affect astrogliosis and neuronal loss. Although animal models of depression only replicate certain clinical features of the condition, they remain valuable for evaluating the complex and varied effects of ketamine. By applying such models, we could demonstrate ketamine\u2019s therapeutic versatility, and also indicate that responses to the treatment may differ across different age groups.<\/jats:p>","DOI":"10.3390\/ijms26083558","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T07:41:51Z","timestamp":1744270911000},"page":"3558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Behavioral and Neuroinflammatory Impact of Ketamine in a Murine Model of Depression and Liver Damage"],"prefix":"10.3390","volume":"26","author":[{"given":"M\u0103d\u0103lina Iuliana","family":"Mu\u0219at","sequence":"first","affiliation":[{"name":"Experimental Research Centre for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana-Maria","family":"Ifrim-Predoi","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smaranda Ioana","family":"Mitran","sequence":"additional","affiliation":[{"name":"Experimental Research Centre for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"},{"name":"Department of Physiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9224-8000","authenticated-orcid":false,"given":"Eugen","family":"Osiac","sequence":"additional","affiliation":[{"name":"Department of Biophysics, University of Medicine and Pharmacy, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5706-8722","authenticated-orcid":false,"given":"Bogdan","family":"C\u0103t\u0103lin","sequence":"additional","affiliation":[{"name":"Experimental Research Centre for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"},{"name":"Department of Physiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jpsychires.2019.08.002","article-title":"Changes in the global burden of depression from 1990 to 2017: Findings from the Global Burden of Disease study","volume":"126","author":"Liu","year":"2020","journal-title":"J. Psychiatr. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.jad.2020.12.035","article-title":"Global trends in the prevalence and incidence of depression:a systematic review and meta-analysis","volume":"281","author":"Wu","year":"2021","journal-title":"J. Affect. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1016\/S0140-6736(18)31948-2","article-title":"Depression","volume":"392","author":"Malhi","year":"2018","journal-title":"Lancet"},{"key":"ref_4","first-page":"10","article-title":"Depression increases the risk for uncontrolled hypertension","volume":"18","author":"Serna","year":"2013","journal-title":"Exp. Clin. Cardiol."},{"key":"ref_5","first-page":"120","article-title":"The association between Diabetes mellitus and Depression","volume":"9","author":"Kobylinska","year":"2016","journal-title":"J. Med. Life"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ma, H., Wang, Y., Xue, Y., Huang, D., Kong, Y., Zhao, X., and Zhang, M. (2019). The effect of Xinkeshu tablets on depression and anxiety symptoms in patients with coronary artery disease: Results from a double-blind, randomized, placebo-controlled study. Biomed. Pharmacother., 112.","DOI":"10.1016\/j.biopha.2019.108639"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S0140-6736(07)61415-9","article-title":"Depression, chronic diseases, and decrements in health: Results from the World Health Surveys","volume":"370","author":"Moussavi","year":"2007","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Xiao, J., Lim, L.K.E., Ng, C.H., Tan, D.J.H., Lim, W.H., Ho, C.S.H., Tan, E.X.X., Sanyal, A.J., and Muthiah, M.D. (2021). Is Fatty Liver Associated With Depression? A Meta-Analysis and Systematic Review on the Prevalence, Risk Factors, and Outcomes of Depression and Non-alcoholic Fatty Liver Disease. Front. Med., 8.","DOI":"10.3389\/fmed.2021.691696"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jad.2021.12.128","article-title":"Association between nonalcoholic fatty liver disease and depression: A systematic review and meta-analysis of observational studies","volume":"301","author":"Gu","year":"2022","journal-title":"J. Affect. Disord."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.psym.2010.12.019","article-title":"Depression in patients with nonalcoholic fatty liver disease and chronic viral hepatitis B and C","volume":"52","author":"Weinstein","year":"2011","journal-title":"Psychosomatics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1002\/hep4.1541","article-title":"Nonalcoholic Fatty Liver Disease Increases the Risk of Anxiety and Depression","volume":"4","author":"Labenz","year":"2020","journal-title":"Hepatol. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e199","DOI":"10.3346\/jkms.2019.34.e199","article-title":"Non-Alcoholic Fatty Liver Disease and Its Association with Depression in Korean General Population","volume":"34","author":"Jung","year":"2019","journal-title":"J. Korean Med. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1017\/S1092852922001043","article-title":"The bidirectional association of nonalcoholic fatty liver disease with depression, bipolar disorder, and schizophrenia","volume":"28","author":"Jawad","year":"2023","journal-title":"CNS Spectr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1111\/apt.12925","article-title":"Review article: Depression and the use of antidepressants in patients with chronic liver disease or liver transplantation","volume":"40","author":"Mullish","year":"2014","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ng, C.H., Xiao, J., Chew, N.W.S., Chin, Y.H., Chan, K.E., Quek, J., Lim, W.H., Tan, D.J.H., Loke, R.W.K., and Tan, C. (2022). Depression in non-alcoholic fatty liver disease is associated with an increased risk of complications and mortality. Front. Med., 9.","DOI":"10.3389\/fmed.2022.985803"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.1111\/liv.14973","article-title":"Impact of major depression and antidepressant use on alcoholic and non-alcoholic fatty liver disease: A population-based study","volume":"41","author":"Shaheen","year":"2021","journal-title":"Liver Int."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhang, S., Pu, Y., Liu, J., Li, L., An, C., Wu, Y., Zhang, W., Zhang, W., Qu, S., and Yan, W. (2024). Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1337749"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1016\/j.drudis.2014.08.017","article-title":"Ketamine: Repurposing and redefining a multifaceted drug","volume":"19","author":"Potter","year":"2014","journal-title":"Drug Discov. Today"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.jad.2024.01.165","article-title":"Ketamine in multiple treatment-resistant depressed inpatients: A naturalistic cohort study","volume":"350","author":"Vestring","year":"2024","journal-title":"J. Affect. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Chrenek, C., Duong, B., Khullar, A., McRee, C., Thomas, R., and Swainson, J. (2023). Use of ketamine for treatment resistant depression: Updated review of literature and practical applications to a community ketamine program in Edmonton, Alberta, Canada. Front. Psychiatry, 14.","DOI":"10.3389\/fpsyt.2023.1283733"},{"key":"ref_21","first-page":"e067194","article-title":"Ketamine for the acute treatment of severe suicidal ideation: Double blind, randomised placebo controlled trial","volume":"376","author":"Abbar","year":"2022","journal-title":"BMJ (Clin. Res. Ed.)"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1176\/appi.ajp.2017.17060647","article-title":"Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial","volume":"175","author":"Grunebaum","year":"2018","journal-title":"Am. J. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1016\/j.pain.2011.03.026","article-title":"Drug-induced liver injury following a repeated course of ketamine treatment for chronic pain in CRPS type 1 patients: A report of 3 cases","volume":"152","author":"Noppers","year":"2011","journal-title":"Pain"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e01239","DOI":"10.1213\/XAA.0000000000001239","article-title":"Substantial Elevation of Liver Enzymes During Ketamine Infusion: A Case Report","volume":"14","author":"Zhu","year":"2020","journal-title":"A A Pract."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1037\/bne0000560","article-title":"A single dose of ketamine enhances early life stress-induced aggression with no effect on fear memory, anxiety-like behavior, or depression-like behavior in mice","volume":"137","author":"Bartsch","year":"2023","journal-title":"Behav. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.neuroscience.2022.12.002","article-title":"The Effects of Acute and Repeated Administration of Ketamine on Memory, Behavior, and Plasma Corticosterone Levels in Female Mice","volume":"512","author":"Acevedo","year":"2023","journal-title":"Neuroscience"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2300","DOI":"10.3748\/wjg.v18.i19.2300","article-title":"Animal models of nonalcoholic fatty liver disease\/nonalcoholic steatohepatitis","volume":"18","author":"Takahashi","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1177\/0960327113506723","article-title":"Dynamics of oxidative\/nitrosative stress in mice with methionine-choline-deficient diet-induced nonalcoholic fatty liver disease","volume":"33","year":"2014","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Brzezinski, R., Levin-Kotler, L., Rabin, N., Zehava, O.-B., Zimmer, Y., Sternfeld, A., Finchelman, J., Unis, R., Lewis, N., and Tepper-Shaihov, O. (2020). Automated thermal imaging for the detection of fatty liver disease. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-72433-5"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1194\/jlr.M800042-JLR200","article-title":"Mechanisms of hepatic steatosis in mice fed a lipogenic methionine choline-deficient diet","volume":"49","author":"Rinella","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Mu\u0219at, M.I., C\u0103t\u0103lin, B., Hadjiargyrou, M., Popa-Wagner, A., and Gre\u0219i\u021b\u0103, A. (2024). Advancing Post-Stroke Depression Research: Insights from Murine Models and Behavioral Analyses. Life, 14.","DOI":"10.3390\/life14091110"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1097\/FBP.0000000000000564","article-title":"The influence of the duration of chronic unpredictable mild stress on the behavioural responses of C57BL\/6J mice","volume":"31","author":"Podkowa","year":"2020","journal-title":"Behav. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Alqurashi, G.K., Hindi, E.A., Zayed, M.A., Abd El-Aziz, G.S., Alturkistani, H.A., Ibrahim, R.F., Al-Thepyani, M.A., Bakhlgi, R., Alzahrani, N.A., and Ashraf, G.M. (2022). The Impact of Chronic Unpredictable Mild Stress-Induced Depression on Spatial, Recognition and Reference Memory Tasks in Mice: Behavioral and Histological Study. Behav. Sci., 12.","DOI":"10.3390\/bs12060166"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"112378","DOI":"10.1016\/j.bbr.2019.112378","article-title":"Increasing doses of ketamine curtail antidepressant responses and suppress associated synaptic signaling pathways","volume":"380","author":"Kim","year":"2020","journal-title":"Behav. Brain Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Khakpai, F., Ebrahimi-Ghiri, M., Alijanpour, S., and Zarrindast, M.-R. (2019). Ketamine-induced antidepressant like effects in mice: A possible involvement of cannabinoid system. Biomed. Pharmacother., 112.","DOI":"10.1016\/j.biopha.2019.108717"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1038\/s41586-023-06624-1","article-title":"Sustained antidepressant effect of ketamine through NMDAR trapping in the LHb","volume":"622","author":"Ma","year":"2023","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"387","DOI":"10.3390\/neurolint13030038","article-title":"Selective Serotonin Reuptake Inhibitors and Adverse Effects: A Narrative Review","volume":"13","author":"Edinoff","year":"2021","journal-title":"Neurol. Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"444","DOI":"10.2174\/1570159X12666140619204251","article-title":"The role of ketamine in treatment-resistant depression: A systematic review","volume":"12","author":"Serafini","year":"2014","journal-title":"Curr. Neuropharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Renemane, L., and Rancans, E. (2024). Sertraline induced acute hepatocellular liver injury in patient with major depressive disorder: A case report. Front. Psychiatry, 15.","DOI":"10.3389\/fpsyt.2024.1456455"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"692","DOI":"10.4065\/74.7.692","article-title":"Acute Hepatitis Due to Fluoxetine Therapy","volume":"74","author":"Cai","year":"1999","journal-title":"Mayo Clin. Proc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"135","DOI":"10.4088\/JCP.v63n0208","article-title":"Hepatotoxicity associated with the new antidepressants","volume":"63","author":"Velasco","year":"2002","journal-title":"J. Clin. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"659","DOI":"10.12688\/f1000research.14344.1","article-title":"Ketamine and rapid-acting antidepressants: A new era in the battle against depression and suicide","volume":"7","author":"Duman","year":"2018","journal-title":"F1000Res"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuro.2022.10.018","article-title":"Ketamine modulates neural stem cell differentiation by regulating TRPC3 expression through the GSK3\u03b2\/\u03b2-catenin pathway","volume":"94","author":"She","year":"2023","journal-title":"NeuroToxicology"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ommati, M.M., Mobasheri, A., Niknahad, H., Rezaei, M., Alidaee, S., Arjmand, A., Mazloomi, S., Abdoli, N., Sadeghian, I., and Sabouri, S. (2023). Low-dose ketamine improves animals\u2019 locomotor activity and decreases brain oxidative stress and inflammation in ammonia-induced neurotoxicity. J. Biochem. Mol. Toxicol., 37.","DOI":"10.1002\/jbt.23468"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1177\/0960327112472990","article-title":"Hepatic effects of ketamine administration for 2 weeks in rats","volume":"33","author":"Kalkan","year":"2014","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1007\/s00213-023-06480-x","article-title":"Oral ketamine may offer a solution to the ketamine conundrum","volume":"240","author":"Dutton","year":"2023","journal-title":"Psychopharmacology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1080\/20961790.2017.1285219","article-title":"Metabolism and metabolomics of ketamine: A toxicological approach","volume":"2","year":"2017","journal-title":"Forensic Sci. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3727\/105221617X15093707969658","article-title":"Updates on Dietary Models of Nonalcoholic Fatty Liver Disease: Current Studies and Insights","volume":"18","author":"Stephenson","year":"2018","journal-title":"Gene Expr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1523\/JNEUROSCI.1316-22.2022","article-title":"NMDA Receptor Activation-Dependent Antidepressant-Relevant Behavioral and Synaptic Actions of Ketamine","volume":"43","author":"Zanos","year":"2023","journal-title":"J. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1038\/s41596-018-0011-z","article-title":"Sucrose preference test for measurement of stress-induced anhedonia in mice","volume":"13","author":"Liu","year":"2018","journal-title":"Nat. Protoc."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Markov, D.D. (2022). Sucrose Preference Test as a Measure of Anhedonic Behavior in a Chronic Unpredictable Mild Stress Model of Depression: Outstanding Issues. Brain Sci., 12.","DOI":"10.3390\/brainsci12101287"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/978-1-4939-8994-2_9","article-title":"The Open Field Test for Measuring Locomotor Activity and Anxiety-Like Behavior","volume":"1916","author":"Kraeuter","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_53","first-page":"814","article-title":"Effects of CUMS on excitatory\/inhibitory balance of hippocampal and prefrontal cortex pyramidal neurons in anxiety-like mice","volume":"38","author":"Zhu","year":"2022","journal-title":"Zhongguo Ying Yong Sheng Li Xue Za Zhi"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Lueptow, L.M. (2017). Novel Object Recognition Test for the Investigation of Learning and Memory in Mice. J. Vis. Exp.","DOI":"10.3791\/55718-v"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/j.1601-183X.2004.00071.x","article-title":"Automated apparatus for quantitation of social approach behaviors in mice","volume":"3","author":"Nadler","year":"2004","journal-title":"Genes. Brain Behav."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1111\/jgh.12897","article-title":"Non-alcoholic fatty liver disease comorbid with major depressive disorder: The pathological features and poor therapeutic efficacy","volume":"30","author":"Tomeno","year":"2015","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1194\/jlr.M600198-JLR200","article-title":"Mice fed a lipogenic methionine-choline-deficient diet develop hypermetabolism coincident with hepatic suppression of SCD-1","volume":"47","author":"Rizki","year":"2006","journal-title":"J. Lipid Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.pbb.2011.10.014","article-title":"Effect of ketamine on exploratory behaviour in BALB\/C and C57BL\/6 mice","volume":"100","author":"Akillioglu","year":"2012","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"113626","DOI":"10.1016\/j.physbeh.2021.113626","article-title":"Ketamine enhances novel object recognition memory reconsolidation via the BDNF\/TrkB pathway in mice","volume":"242","author":"Fan","year":"2021","journal-title":"Physiol. Behav."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Morega, S., C\u0103t\u0103lin, B., Simionescu, C.E., Sapalidis, K., and Rogoveanu, I. (2021). Cerebrolysin Prevents Brain Injury in a Mouse Model of Liver Damage. Brain Sci., 11.","DOI":"10.3390\/brainsci11121622"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1007\/s12640-017-9759-0","article-title":"Comparison of the Psychopharmacological Effects of Tiletamine and Ketamine in Rodents","volume":"32","author":"Popik","year":"2017","journal-title":"Neurotox. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.biopsych.2013.12.014","article-title":"Effects of striatal \u0394FosB overexpression and ketamine on social defeat stress-induced anhedonia in mice","volume":"76","author":"Donahue","year":"2014","journal-title":"Biol. Psychiatry"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1093\/cercor\/bhy070","article-title":"Prefrontal Oxytocin is Involved in Impairments in Prefrontal Plasticity and Social Memory Following Acute Exposure to High Fat Diet in Juvenile Animals","volume":"29","author":"Yaseen","year":"2019","journal-title":"Cereb. Cortex"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Hayashi, R., Kasahara, Y., Hidema, S., Fukumitsu, S., Nakagawa, K., and Nishimori, K. (2020). Oxytocin Ameliorates Impaired Behaviors of High Fat Diet-Induced Obese Mice. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00379"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/s41366-019-0468-z","article-title":"Saturated fatty acid is a principal cause of anxiety-like behavior in diet-induced obese rats in relation to serum lysophosphatidyl choline level","volume":"44","author":"Nakajima","year":"2020","journal-title":"Int. J. Obes."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1111\/bph.13343","article-title":"High-fat diet-induced metabolic disorders impairs 5-HT function and anxiety-like behavior in mice","volume":"173","author":"Zemdegs","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.physbeh.2017.06.007","article-title":"The ketogenic diet affects the social behavior of young male rats","volume":"179","author":"Nowicka","year":"2017","journal-title":"Physiol. Behav."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1037\/bne0000368","article-title":"Gestational exposure to a ketogenic diet increases sociability in CD-1 mice","volume":"134","author":"Arqoub","year":"2020","journal-title":"Behav. Neurosci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.physbeh.2016.04.001","article-title":"Ketogenic diet exposure during the juvenile period increases social behaviors and forebrain neural activation in adult Engrailed 2 null mice","volume":"161","author":"Verpeut","year":"2016","journal-title":"Physiol. Behav."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"136443","DOI":"10.1016\/j.neulet.2021.136443","article-title":"A combination of ketogenic diet and voluntary exercise ameliorates anxiety and depression-like behaviors in Balb\/c mice","volume":"770","author":"Gumus","year":"2022","journal-title":"Neurosci. Lett."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.1038\/s41467-022-30386-5","article-title":"Ketamine activates adult-born immature granule neurons to rapidly alleviate depression-like behaviors in mice","volume":"13","author":"Rawat","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1007\/s13365-019-00721-6","article-title":"Astrocyte activation and altered metabolism in normal aging, age-related CNS diseases, and HAND","volume":"25","author":"Cotto","year":"2019","journal-title":"J. Neurovirol"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"5","DOI":"10.13188\/2332-3469.1000048","article-title":"Astrocyte Activation is A Potential Mechanism Underlying Depressed Mood and Apathy in People with HIV","volume":"9","author":"Ellis","year":"2022","journal-title":"J. Neurol. Psychol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Lullau, A.P.M., Haga, E.M.W., Ronold, E.H., and Dwyer, G.E. (2023). Antidepressant mechanisms of ketamine: A review of actions with relevance to treatment-resistance and neuroprogression. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1223145"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Soko\u0142owska, P., Seweryn Karbownik, M., J\u00f3\u017awiak-B\u0119benista, M., Dobielska, M., Kowalczyk, E., and Wiktorowska-Owczarek, A. (2023). Antidepressant mechanisms of ketamine\u2019s action: NF-\u03baB in the spotlight. Biochem. Pharmacol., 218.","DOI":"10.1016\/j.bcp.2023.115918"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Wu, S., Xie, L., Yu, S., Zhang, L., Liu, C., Zhou, W., and Yu, T. (2019). Ketamine Within Clinically Effective Range Inhibits Glutamate Transmission From Astrocytes to Neurons and Disrupts Synchronization of Astrocytic SICs. Front. Cell Neurosci., 13.","DOI":"10.3389\/fncel.2019.00240"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"283","DOI":"10.30773\/pi.2019.0189","article-title":"NLRP1-Mediated Antidepressant Effect of Ketamine in Chronic Unpredictable Mild Stress Model in Rats","volume":"17","author":"Yalcinkaya","year":"2020","journal-title":"Psychiatry Investig."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1038\/s41380-022-01520-y","article-title":"Dysregulation of adult hippocampal neuroplasticity in major depression: Pathogenesis and therapeutic implications","volume":"27","author":"Tartt","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/s41398-024-02928-6","article-title":"Molecular signatures of astrocytes and microglia maladaptive responses to acute stress are rescued by a single administration of ketamine in a rodent model of PTSD","volume":"14","author":"Valenza","year":"2024","journal-title":"Transl. Psychiatry"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1093\/bja\/aei256","article-title":"Effects of ketamine and propofol on inflammatory responses of primary glial cell cultures stimulated with lipopolysaccharide","volume":"95","author":"Shibakawa","year":"2005","journal-title":"BJA Br. J. Anaesth."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e000678","DOI":"10.1136\/bmjgast-2021-000678","article-title":"Factors associated with engagement and adherence to a low-energy diet to promote 10% weight loss in patients with clinically significant non-alcoholic fatty liver disease","volume":"8","author":"Scragg","year":"2021","journal-title":"BMJ Open Gastroenterol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5235","DOI":"10.12998\/wjcc.v8.i21.5235","article-title":"Essential phospholipids for nonalcoholic fatty liver disease associated with metabolic syndrome: A systematic review and network meta-analysis","volume":"8","author":"Dajani","year":"2020","journal-title":"World J. Clin. Cases"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Mu\u0219at, M.I., Militaru, F., Gheorman, V., Udri\u0219toiu, I., Mitran, S.I., and C\u0103t\u0103lin, B. (2024). Moderate Alcohol Consumption Increases the Risk of Clinical Relapse in Male Depressed Patients Treated with Serotonin-Norepinephrine Reuptake Inhibitors. Diagnostics, 14.","DOI":"10.3390\/diagnostics14111140"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Mu\u0219at, M.I., Militaru, F., Udri\u0219toiu, I., Mitran, S.I., and C\u0103t\u0103lin, B. (2024). Alcohol Consumption Is a Coping Mechanism for Male Patients with Severe Anxiety Disorders Treated with Antidepressants Monotherapy. J. Clin. Med., 13.","DOI":"10.3390\/jcm13092723"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Mu\u0219at, M.I., Mitran, S.I., Udri\u0219toiu, I., Albu, C.V., and C\u0103t\u0103lin, B. (2024). The impact of stress on the behavior of C57BL\/6 mice with liver injury: A comparative study. Front. Behav. Neurosci., 18.","DOI":"10.3389\/fnbeh.2024.1358964"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"149123","DOI":"10.1016\/j.brainres.2024.149123","article-title":"The chronic unpredictable mild stress (CUMS) Paradigm: Bridging the gap in depression research from bench to bedside","volume":"1843","author":"Sharma","year":"2024","journal-title":"Brain Res."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Pa\u0142ucha-Poniewiera, A., Podkowa, K., and Rafa\u0142o-Uli\u0144ska, A. (2021). The group II mGlu receptor antagonist LY341495 induces a rapid antidepressant-like effect and enhances the effect of ketamine in the chronic unpredictable mild stress model of depression in C57BL\/6J mice. Prog. Neuropsychopharmacol. Biol. Psychiatry, 109.","DOI":"10.1016\/j.pnpbp.2020.110239"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Morega, S., Gresita, A., Mitran, S.I., Musat, M.I., Boboc, I.K.S., Gheorman, V., Udristoiu, I., Albu, C.V., Streba, C.T., and Catalin, B. (2022). Cerebrolysin Use in Patients with Liver Damage-A Translational Study. Life, 12.","DOI":"10.3390\/life12111791"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Gaignier, F., Legrand-Frossi, C., Stragier, E., Mathiot, J., Merlin, J.-L., Cohen-Salmon, C., Lanfumey, L., and Frippiat, J.-P. (2018). A Model of Chronic Exposure to Unpredictable Mild Socio-Environmental Stressors Replicates Some Spaceflight-Induced Immunological Changes. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00514"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s12967-023-03993-z","article-title":"Matrine alleviates depressive-like behaviors via modulating microbiota-gut-brain axis in CUMS-induced mice","volume":"21","author":"Zhang","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Wang, G., Lei, C., Tian, Y., Wang, Y., Zhang, L., and Zhang, R. (2019). Rb1, the Primary Active Ingredient in Panax ginseng C.A. Meyer, Exerts Antidepressant-Like Effects via the BDNF\u2013Trkb\u2013CREB Pathway. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01034"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.fitote.2014.06.007","article-title":"Emodin opposes chronic unpredictable mild stress induced depressive-like behavior in mice by upregulating the levels of hippocampal glucocorticoid receptor and brain-derived neurotrophic factor","volume":"98","author":"Li","year":"2014","journal-title":"Fitoterapia"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"157","DOI":"10.5625\/lar.2017.33.2.157","article-title":"Comparative study of fatty liver induced by methionine and choline-deficiency in C57BL\/6N mice originating from three different sources","volume":"33","author":"Kim","year":"2017","journal-title":"Lab. Anim. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.bbr.2010.04.041","article-title":"Strain differences in the chronic mild stress animal model of depression","volume":"213","author":"Wu","year":"2010","journal-title":"Behav. Brain Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1177\/0271678X21996177","article-title":"Reduction of neuroinflammation alleviated mouse post bone fracture and stroke memory dysfunction","volume":"41","author":"Huo","year":"2021","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Tsao, C.H., Wu, K.Y., Su, N.C., Edwards, A., and Huang, G.J. (2023). The influence of sex difference on behavior and adult hippocampal neurogenesis in C57BL\/6 mice. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-44360-8"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Kaidanovich-Beilin, O., Lipina, T., Vukobradovic, I., Roder, J., and Woodgett, J. (2011). Assessment of Social Interaction Behaviors. J. Vis. Exp. JoVE, 2011.","DOI":"10.3791\/2473-v"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jchemneu.2017.08.007","article-title":"The in situ morphology of microglia is highly sensitive to the mode of tissue fixation","volume":"86","author":"Stopper","year":"2017","journal-title":"J. Chem. Neuroanat."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Godeanu, S., Mu\u0219at, M.I., Scheller, A., Osiac, E., and C\u0103t\u0103lin, B. (2025). Minimal differences observed when comparing the morphological profiling of microglia obtained by confocal laser scanning and optical sectioning microscopy. Front. Neuroanat., 18.","DOI":"10.3389\/fnana.2024.1507140"},{"key":"ref_100","first-page":"577","article-title":"Morphological Differences in Hippocampal Microglia in C57BL\/6N Mice with Liver Injury and Depressive-Like Behavior","volume":"50","author":"Nedelea","year":"2024","journal-title":"Curr. Health Sci. J."},{"key":"ref_101","first-page":"546","article-title":"Depressive-Like Behavior and Liver Damage Generate Behavioral and Cortical Microglial Morphological Differences in Mice","volume":"50","author":"Nedelea","year":"2024","journal-title":"Curr. Health Sci. J."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"679","DOI":"10.47162\/RJME.65.4.15","article-title":"Acute liver damage generates age independent microglia morphology changes in mice","volume":"65","author":"Nedelea","year":"2024","journal-title":"Rom. J. Morphol. Embryol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3558\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:12:08Z","timestamp":1760029928000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3558"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,10]]},"references-count":102,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26083558"],"URL":"https:\/\/doi.org\/10.3390\/ijms26083558","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,10]]}}}