{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:10:32Z","timestamp":1778274632149,"version":"3.51.4"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2027,4,3]],"date-time":"2027-04-03T00:00:00Z","timestamp":1806710400000},"content-version":"am","delay-in-days":306,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP24K18367"],"award-info":[{"award-number":["JP24K18367"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neurochemistry International"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1016\/j.neuint.2026.106152","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T07:59:26Z","timestamp":1775030366000},"page":"106152","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["AICAR improves depression-like behaviors and is associated with hippocampal AMPK activation and modulation of neurogenesis and neuroinflammation in a microbiota disruption model"],"prefix":"10.1016","volume":"196","author":[{"given":"Kohei","family":"Takahashi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiro","family":"Kurokawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranmaru","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Takeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0088-282X","authenticated-orcid":false,"given":"Minoru","family":"Tsuji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.neuint.2026.106152_bib1","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nrn.2017.45","article-title":"Adult hippocampal neurogenesis and cognitive flexibility - linking memory and mood","volume":"18","author":"Anacker","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.neuint.2026.106152_bib2","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.coph.2006.08.009","article-title":"Role of neurotrophic factors in depression","volume":"7","author":"Castr\u00e9n","year":"2007","journal-title":"Curr. Opin. Pharmacol."},{"key":"10.1016\/j.neuint.2026.106152_bib3","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.brainresbull.2022.02.004","article-title":"Brain-gut-microbiota axis in depression: a historical overview and future directions","volume":"182","author":"Chang","year":"2022","journal-title":"Brain Res. Bull."},{"key":"10.1016\/j.neuint.2026.106152_bib4","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nrn3346","article-title":"Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour","volume":"13","author":"Cryan","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.neuint.2026.106152_bib5","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.maturitas.2016.11.016","article-title":"Influence of equol and resveratrol supplementation on health-related quality of life in menopausal women: a randomized, placebo-controlled study","volume":"96","author":"Davinelli","year":"2017","journal-title":"Maturitas"},{"key":"10.1016\/j.neuint.2026.106152_bib6","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.biopsych.2006.02.013","article-title":"A neurotrophic model for stress-related mood disorders","volume":"59","author":"Duman","year":"2006","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.neuint.2026.106152_bib7","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ynstr.2017.03.001","article-title":"Stress & the gut-brain axis: regulation by the microbiome","volume":"7","author":"Foster","year":"2017","journal-title":"Neurobiol. Stress"},{"key":"10.1016\/j.neuint.2026.106152_bib8","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.bbi.2017.09.001","article-title":"Antibiotic-induced microbiota perturbation causes gut endocannabinoidome changes, hippocampal neuroglial reorganization and depression in mice","volume":"67","author":"Guida","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"10.1016\/j.neuint.2026.106152_bib9","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1111\/1440-1681.12265","article-title":"Metformin may produce antidepressant effects through improvement of cognitive function among depressed patients with diabetes mellitus","volume":"41","author":"Guo","year":"2014","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"10.1016\/j.neuint.2026.106152_bib10","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1007\/s00018-022-04471-3","article-title":"5-Aminosalicylic acid ameliorates dextran sulfate sodium-induced colitis in mice by modulating gut microbiota and bile acid metabolism","volume":"79","author":"Huang","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.neuint.2026.106152_bib11","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuint.2021.105213","article-title":"Activation of 5-HT(1A) receptor reduces abnormal emotionality in stress-maladaptive mice by alleviating decreased myelin protein in the ventral hippocampus","volume":"151","author":"Kurokawa","year":"2021","journal-title":"Neurochem. Int."},{"key":"10.1016\/j.neuint.2026.106152_bib12","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0027662","article-title":"The intestinal flora is required to support antibody responses to systemic immunization in infant and germ free mice","volume":"6","author":"Lamouse-Smith","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.neuint.2026.106152_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2023.104527","article-title":"Gut microbiota and its metabolites in depression: from pathogenesis to treatment","volume":"90","author":"Liu","year":"2023","journal-title":"EBioMedicine"},{"key":"10.1016\/j.neuint.2026.106152_bib14","article-title":"Akebia saponin D protects hippocampal neurogenesis from microglia-mediated inflammation and ameliorates depressive-like behaviors and cognitive impairment in mice through the PI3K-Akt pathway","volume":"13","author":"Liu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.neuint.2026.106152_bib15","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1038\/nn.4086","article-title":"Mechanisms of stress in the brain","volume":"18","author":"McEwen","year":"2015","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.neuint.2026.106152_bib16","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2020.583291","article-title":"Scabronine G methyl ester improves memory-related behavior and enhances hippocampal cell proliferation and long-term potentiation via the BDNF-CREB pathway in olfactory bulbectomized mice","volume":"11","author":"Nakagawasai","year":"2020","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.neuint.2026.106152_bib17","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.jphs.2022.01.009","article-title":"ERK5 inhibitor BIX02189 attenuates methamphetamine-induced hyperactivity by modulating microglial activation in the striatum","volume":"148","author":"Nakagawasai","year":"2022","journal-title":"J. Pharmacol. Sci."},{"key":"10.1016\/j.neuint.2026.106152_bib18","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.jphs.2020.01.002","article-title":"Liver hydrolysate improves depressive-like behavior in olfactory bulbectomized mice: involvement of hippocampal neurogenesis through the AMPK\/BDNF\/CREB pathway","volume":"143","author":"Nakagawasai","year":"2020","journal-title":"J. Pharmacol. Sci."},{"key":"10.1016\/j.neuint.2026.106152_bib19","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbr.2020.112640","article-title":"Liver hydrolysate prevents depressive-like behavior in an animal model of colitis: involvement of hippocampal neurogenesis via the AMPK\/BDNF pathway","volume":"390","author":"Nakagawasai","year":"2020","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.neuint.2026.106152_bib20","article-title":"AMPK activation improves depression-like symptoms in olfactory bulbectomized mice by regulating microglia M1\/M2 polarization in the hippocampus","volume":"46","author":"Odaira-Satoh","year":"2025","journal-title":"Brain Behav Immun Health"},{"key":"10.1016\/j.neuint.2026.106152_bib21","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.neuropharm.2019.03.026","article-title":"Mechanisms underpinning AMP-activated protein kinase-related effects on behavior and hippocampal neurogenesis in an animal model of depression","volume":"150","author":"Odaira","year":"2019","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.neuint.2026.106152_bib22","series-title":"The Mouse Brain in Stereotaxic Coordinates","author":"Paxinos","year":"2001"},{"key":"10.1016\/j.neuint.2026.106152_bib23","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1084\/jem.128.1.97","article-title":"Alterations in the mouse cecum and its flora produced by antibacterial drugs","volume":"128","author":"Savage","year":"1968","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.neuint.2026.106152_bib24","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1590\/S1516-44462005000300017","article-title":"[Neurogenesis and depression: etiology or new illusion?]","volume":"27","author":"Scorza","year":"2005","journal-title":"Br. J. Psychiatry"},{"key":"10.1016\/j.neuint.2026.106152_bib25","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.2174\/1871527313666141130223723","article-title":"Hippocampal neurogenesis, neurotrophic factors and depression: possible therapeutic targets?","volume":"13","author":"Serafini","year":"2014","journal-title":"CNS Neurol. Disord. - Drug Targets"},{"key":"10.1016\/j.neuint.2026.106152_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.cpr.2020.101943","article-title":"The gut microbiota in anxiety and depression - a systematic review","volume":"83","author":"Simpson","year":"2021","journal-title":"Clin. Psychol. Rev."},{"key":"10.1016\/j.neuint.2026.106152_bib27","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/nature10287","article-title":"Adult hippocampal neurogenesis buffers stress responses and depressive behaviour","volume":"476","author":"Snyder","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.neuint.2026.106152_bib28","article-title":"Brexpiprazole prevents colitis-induced depressive-like behavior through myelination in the prefrontal cortex","volume":"121","author":"Takahashi","year":"2023","journal-title":"Prog. Neuro Psychopharmacol. Biol. Psychiatr."},{"key":"10.1016\/j.neuint.2026.106152_bib29","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.jpsychires.2022.01.047","article-title":"Antidepressant effects of Enterococcus faecalis 2001 through the regulation of prefrontal cortical myelination via the enhancement of CREB\/BDNF and NF-kappaB p65\/LIF\/STAT3 pathways in olfactory bulbectomized mice","volume":"148","author":"Takahashi","year":"2022","journal-title":"J. Psychiatr. Res."},{"key":"10.1016\/j.neuint.2026.106152_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuint.2021.105112","article-title":"Disturbance of prefrontal cortical myelination in olfactory bulbectomized mice is associated with depressive-like behavior","volume":"148","author":"Takahashi","year":"2021","journal-title":"Neurochem. Int."},{"key":"10.1016\/j.neuint.2026.106152_bib31","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.neures.2022.06.001","article-title":"Correlation between the reduction in hippocampal SirT2 expression and depressive-like behaviors and neurological abnormalities in olfactory bulbectomized mice","volume":"182","author":"Takahashi","year":"2022","journal-title":"Neurosci. Res."},{"key":"10.1016\/j.neuint.2026.106152_bib32","article-title":"Hippocampal and gut AMPK activation attenuates enterocolitis-like symptoms and co-occurring depressive-like behavior in ulcerative colitis model mice: involvement of brain-gut autophagy","author":"Takahashi","year":"2023","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.neuint.2026.106152_bib33","doi-asserted-by":"crossref","DOI":"10.1016\/j.physbeh.2020.112997","article-title":"Antidementia effects of Enterococcus faecalis 2001 are associated with enhancement of hippocampal neurogenesis via the ERK-CREB-BDNF pathway in olfactory bulbectomized mice","volume":"223","author":"Takahashi","year":"2020","journal-title":"Physiol. Behav."},{"key":"10.1016\/j.neuint.2026.106152_bib34","doi-asserted-by":"crossref","DOI":"10.1016\/j.neulet.2024.137711","article-title":"Repeated antibiotic drug treatment negatively affects memory function and glutamatergic nervous system of the hippocampus in mice","volume":"825","author":"Takahashi","year":"2024","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.neuint.2026.106152_bib35","doi-asserted-by":"crossref","DOI":"10.1016\/j.neulet.2025.138131","article-title":"Repeated exposure to antibiotics exhibits anxiety-like behaviors with a reduction in neurogenesis in the ventral hippocampus of dentate gyrus","volume":"849","author":"Takahashi","year":"2025","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.neuint.2026.106152_bib36","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s11481-025-10232-3","article-title":"Activation of hippocampal ACE2 prevents the dysbiosis-induced depression-like behavior in mice by enhanced neurogenesis and neuroprotection via mas receptor","volume":"20","author":"Takahashi","year":"2025","journal-title":"J. Neuroimmune Pharmacol."},{"key":"10.1016\/j.neuint.2026.106152_bib37","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.neuropharm.2018.04.013","article-title":"Memantine ameliorates depressive-like behaviors by regulating hippocampal cell proliferation and neuroprotection in olfactory bulbectomized mice","volume":"137","author":"Takahashi","year":"2018","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.neuint.2026.106152_bib38","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.euroneuro.2017.08.071","article-title":"Time-dependent role of prefrontal cortex and hippocampus on cognitive improvement by aripiprazole in olfactory bulbectomized mice","volume":"27","author":"Takahashi","year":"2017","journal-title":"Eur. Neuropsychopharmacol."},{"key":"10.1016\/j.neuint.2026.106152_bib39","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1186\/s12974-019-1580-7","article-title":"Effect of Enterococcus faecalis 2001 on colitis and depressive-like behavior in dextran sulfate sodium-treated mice: involvement of the brain-gut axis","volume":"16","author":"Takahashi","year":"2019","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.neuint.2026.106152_bib40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuropharm.2019.02.034","article-title":"Prenatal treatment with methylazoxymethanol acetate as a neurodevelopmental disruption model of schizophrenia in mice","volume":"150","author":"Takahashi","year":"2019","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.neuint.2026.106152_bib41","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuint.2024.105723","article-title":"Polarization to M1-type microglia in the hippocampus is involved in depression-like behavior in a mouse model of olfactory dysfunction","volume":"175","author":"Takahashi","year":"2024","journal-title":"Neurochem. Int."},{"key":"10.1016\/j.neuint.2026.106152_bib42","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13041-021-00759-w","article-title":"Antibiotics-induced intestinal dysbacteriosis caused behavioral alternations and neuronal activation in different brain regions in mice","volume":"14","author":"Wang","year":"2021","journal-title":"Mol. Brain"},{"key":"10.1016\/j.neuint.2026.106152_bib43","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1186\/s12974-023-02964-x","article-title":"Neuroinflammation, memory, and depression: new approaches to hippocampal neurogenesis","volume":"20","author":"Wu","year":"2023","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.neuint.2026.106152_bib44","doi-asserted-by":"crossref","DOI":"10.3390\/nu15143258","article-title":"The role of gut microbiota in anxiety, depression, and other mental disorders as well as the protective effects of dietary components","volume":"15","author":"Xiong","year":"2023","journal-title":"Nutrients"},{"key":"10.1016\/j.neuint.2026.106152_bib45","article-title":"Metformin-mediated intestinal AMPK activation ameliorates PCOS through gut microbiota modulation and metabolic pathways","volume":"16","author":"Xu","year":"2025","journal-title":"Front. Endocrinol."},{"key":"10.1016\/j.neuint.2026.106152_bib46","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.bbrc.2017.08.034","article-title":"The endotoxemia cardiac dysfunction is attenuated by AMPK\/mTOR signaling pathway regulating autophagy","volume":"492","author":"Zhang","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["Neurochemistry International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0197018626000434?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0197018626000434?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T20:18:30Z","timestamp":1778271510000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0197018626000434"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":46,"alternative-id":["S0197018626000434"],"URL":"https:\/\/doi.org\/10.1016\/j.neuint.2026.106152","relation":{},"ISSN":["0197-0186"],"issn-type":[{"value":"0197-0186","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"AICAR improves depression-like behaviors and is associated with hippocampal AMPK activation and modulation of neurogenesis and neuroinflammation in a microbiota disruption model","name":"articletitle","label":"Article Title"},{"value":"Neurochemistry International","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.neuint.2026.106152","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"106152"}}