{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:43:09Z","timestamp":1786542189938,"version":"build-2736575974"},"reference-count":106,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016350","name":"Sichuan Provincial Administration of Traditional Chinese Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100016350","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82074576"],"award-info":[{"award-number":["82074576"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neuroscience &amp; Biobehavioral Reviews"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.neubiorev.2026.106847","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T22:17:57Z","timestamp":1783203477000},"page":"106847","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Irisin and anxiety-like behaviors: Mechanistic integration of peripheral\u2013central crosstalk, neuroinflammation, and neural plasticity"],"prefix":"10.1016","volume":"189","author":[{"given":"Hongguo","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaojie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxiao","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9104-6431","authenticated-orcid":false,"given":"Yushi","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.neubiorev.2026.106847_bib1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S2215-0366(21)00395-3","article-title":"Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019","volume":"9","author":"2019 Mental Disorders Collaborators","year":"2022","journal-title":"Lancet Psychiatry"},{"key":"10.1016\/j.neubiorev.2026.106847_bib2","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1007\/s00210-023-02726-9","article-title":"Irisin\/PGC-1\u03b1\/FNDC5 pathway in Parkinson\u2019s disease: truth under the throes","volume":"397","author":"Ali","year":"2024","journal-title":"Naunyn. Schmiede Arch. Pharmacol."},{"key":"10.1016\/j.neubiorev.2026.106847_bib3","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/da.22711","article-title":"Treatment gap for anxiety disorders is global: results of the World Mental Health Surveys in 21 countries","volume":"35","author":"Alonso","year":"2018","journal-title":"Depress Anxiety"},{"key":"10.1016\/j.neubiorev.2026.106847_bib4","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s42977-025-00287-x","article-title":"Evaluation of irisin levels in plasma, skeletal muscle, and brain tissues after voluntary or regular exercise in adolescent male rats exposed to chronic social isolation","volume":"76","author":"Arslankiran","year":"2025","journal-title":"Biol. Futur."},{"key":"10.1016\/j.neubiorev.2026.106847_bib5","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.tem.2022.06.003","article-title":"Irisin, a fascinating field in our times","volume":"33","author":"Bao","year":"2022","journal-title":"Trends Endocrinol. Metab. TEM"},{"key":"10.1016\/j.neubiorev.2026.106847_bib6","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1111\/jcmm.14811","article-title":"Irisin reverses intestinal epithelial barrier dysfunction during intestinal injury via binding to the integrin \u03b1V\u03b25 receptor","volume":"24","author":"Bi","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"10.1016\/j.neubiorev.2026.106847_bib7","doi-asserted-by":"crossref","first-page":"8233","DOI":"10.2174\/0109298673356125250409182218","article-title":"The gut microbiota-anxiety connection: evidence, mechanisms, and therapeutic strategies","volume":"32","author":"Bj\u00f8rklund","year":"2025","journal-title":"Curr. Med. Chem."},{"key":"10.1016\/j.neubiorev.2026.106847_bib8","unstructured":"Borukhin J.A., Kang E., Tomas R.F., n.d. Behavioral and metabolic effects of extended hippocampal overexpression of the myokine Irisin in an Alzheimer\u2019s Disease mouse model | bioRxiv [WWW Document]. URL \u3008https:\/\/www.biorxiv.org\/content\/10.1101\/2024.12.16.628747v1\u3009 (accessed 6.3.26)."},{"key":"10.1016\/j.neubiorev.2026.106847_bib9","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nature10777","article-title":"A PGC1-\u03b1-dependent myokine that drives brown-fat-like development of white fat and thermogenesis","volume":"481","author":"Bostr\u00f6m","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.neubiorev.2026.106847_bib10","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/dmrr.2660","article-title":"Irisin, an exercise-induced myokine as a metabolic regulator: an updated narrative review","volume":"32","author":"Chen","year":"2016","journal-title":"Diabetes Metab. Res. Rev."},{"key":"10.1016\/j.neubiorev.2026.106847_bib11","first-page":"797","article-title":"Effects of central fibroblast growth factor 21 and irisin in anxiety-like behavior","volume":"31","author":"Chiavaroli","year":"2017","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"10.1016\/j.neubiorev.2026.106847_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2024.103101","article-title":"Aerobic exercise attenuates LPS-induced cognitive dysfunction by reducing oxidative stress, glial activation, and neuroinflammation","volume":"71","author":"Choi","year":"2024","journal-title":"Redox Biol."},{"key":"10.1016\/j.neubiorev.2026.106847_bib13","doi-asserted-by":"crossref","DOI":"10.1126\/science.aan8821","article-title":"Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer\u2019s mouse model","volume":"361","author":"Choi","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.neubiorev.2026.106847_bib14","doi-asserted-by":"crossref","first-page":"14686","DOI":"10.3390\/ijms241914686","article-title":"Physical exercise as disease-modifying alternative against Alzheimer\u2019s disease: a gut-muscle-brain partnership","volume":"24","author":"Cutuli","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.neubiorev.2026.106847_bib15","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/ana.26946","article-title":"Irisin levels in cerebrospinal fluid correlate with biomarkers and clinical dementia scores in Alzheimer Disease","volume":"96","author":"Dicarlo","year":"2024","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.neubiorev.2026.106847_bib16","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.neuroscience.2013.02.050","article-title":"Irisin-immunoreactivity in neural and non-neural cells of the rodent","volume":"240","author":"Dun","year":"2013","journal-title":"Neuroscience"},{"key":"10.1016\/j.neubiorev.2026.106847_bib17","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-024-76658-6","article-title":"Irisin promotes intestinal epithelial cell proliferation via Wnt\/\u03b2-catenin and focal adhesion kinase signaling pathways","volume":"14","author":"Gaowa","year":"2024","journal-title":"Sci. Rep."},{"key":"10.1016\/j.neubiorev.2026.106847_bib18","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.jpsychires.2025.09.058","article-title":"Irisin: Its significance in the diagnosis and treatment of post-stroke depression","volume":"191","author":"Han","year":"2025","journal-title":"J. Psychiatr. Res."},{"key":"10.1016\/j.neubiorev.2026.106847_bib19","doi-asserted-by":"crossref","DOI":"10.1002\/alz70855_104063","article-title":"Irisin attenuates astrocyte activation and rescues memory in Alzheimer model mice","volume":"21","author":"Heimfarth","year":"2025","journal-title":"Alzheimers Dement."},{"key":"10.1016\/j.neubiorev.2026.106847_bib20","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1016\/j.neubiorev.2013.03.010","article-title":"Effects of diabetes on hippocampal neurogenesis: links to cognition and depression","volume":"37","author":"Ho","year":"2013","journal-title":"Neurosci. Biobehav. Rev."},{"key":"10.1016\/j.neubiorev.2026.106847_bib21","first-page":"195","article-title":"The exercise-induced myokine irisin does not show an association with depressiveness, anxiety and perceived stress in obese women","volume":"67","author":"Hofmann","year":"2016","journal-title":"J. Physiol. Pharmacol. Off. J. Pol. Physiol. Soc."},{"key":"10.1016\/j.neubiorev.2026.106847_bib22","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1126\/science.aad8373","article-title":"Complement and microglia mediate early synapse loss in Alzheimer mouse models","volume":"352","author":"Hong","year":"2016","journal-title":"Science"},{"key":"10.1016\/j.neubiorev.2026.106847_bib23","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-023-43684-9","article-title":"Exploring the role of esketamine in alleviating depressive symptoms in mice via the PGC-1\u03b1\/irisin\/ERK1\/2 signaling pathway","volume":"13","author":"Hu","year":"2023","journal-title":"Sci. Rep."},{"key":"10.1016\/j.neubiorev.2026.106847_bib24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7555\/JBR.37.20230133","article-title":"Irisin\/BDNF signaling in the muscle-brain axis and circadian system: a review","volume":"38","author":"Inyushkin","year":"2023","journal-title":"J. Biomed. Res."},{"key":"10.1016\/j.neubiorev.2026.106847_bib25","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1038\/s42255-021-00438-z","article-title":"Exercise hormone irisin is a critical regulator of cognitive function","volume":"3","author":"Islam","year":"2021","journal-title":"Nat. Metab."},{"key":"10.1016\/j.neubiorev.2026.106847_bib26","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1037\/bul0000111","article-title":"Anxiety and depression as bidirectional risk factors for one another: a meta-analysis of longitudinal studies","volume":"143","author":"Jacobson","year":"2017","journal-title":"Psychol. Bull."},{"key":"10.1016\/j.neubiorev.2026.106847_bib27","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1007\/s11011-023-01202-w","article-title":"Irisin attenuates ethanol-induced behavioral deficits in mice through activation of Nrf2 and inhibition of NF-KB pathways","volume":"38","author":"Jiang","year":"2023","journal-title":"Metab. Brain Dis."},{"key":"10.1016\/j.neubiorev.2026.106847_bib28","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1007\/s11064-014-1462-4","article-title":"Acute restraint stress impairs induction of long-term potentiation by activating GSK-3\u03b2","volume":"40","author":"Jin","year":"2015","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.neubiorev.2026.106847_bib29","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2021.649929","article-title":"Multiple roles in neuroprotection for the exercise derived myokine irisin","volume":"13","author":"Jodeiri Farshbaf","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.neubiorev.2026.106847_bib30","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1037\/bne0000367","article-title":"Hippocampal injection of the exercise-induced myokine irisin suppresses acute stress-induced neurobehavioral impairment in a sex-dependent manner","volume":"134","author":"Jodeiri Farshbaf","year":"2020","journal-title":"Behav. Neurosci."},{"key":"10.1016\/j.neubiorev.2026.106847_bib31","doi-asserted-by":"crossref","first-page":"3619","DOI":"10.1016\/j.neuron.2023.08.012","article-title":"Irisin reduces amyloid-\u03b2 by inducing the release of neprilysin from astrocytes following downregulation of ERK-STAT3 signaling","volume":"111","author":"Kim","year":"2023","journal-title":"Neuron"},{"key":"10.1016\/j.neubiorev.2026.106847_bib32","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1016\/j.cell.2018.10.025","article-title":"Irisin mediates effects on bone and fat via \u03b1V integrin receptors","volume":"175","author":"Kim","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.neubiorev.2026.106847_bib33","doi-asserted-by":"crossref","first-page":"574","DOI":"10.2174\/1570159X15666170913110426","article-title":"Neuroinflammation and the immune-kynurenine pathway in anxiety disorders","volume":"16","author":"Kim","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"10.1016\/j.neubiorev.2026.106847_bib34","first-page":"50","article-title":"Critical Role of the Endothelial \u03b1V\/\u03b25 integrin receptor signaling pathway in promoting irisin-induced hippocampal BDNF Expression","volume":"63","author":"Leger","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.neubiorev.2026.106847_bib35","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.47106","article-title":"TMEM16B regulates anxiety-related behavior and GABAergic neuronal signaling in the central lateral amygdala","volume":"8","author":"Li","year":"2019","journal-title":"eLife"},{"key":"10.1016\/j.neubiorev.2026.106847_bib36","doi-asserted-by":"crossref","DOI":"10.1523\/ENEURO.0256-22.2023","article-title":"Brain FNDC5\/Irisin expression in patients and mouse models of major depression","volume":"10","author":"Lima-Filho","year":"2023","journal-title":"eNeuro"},{"key":"10.1016\/j.neubiorev.2026.106847_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.brainres.2023.148537","article-title":"Fndc5\/irisin deficiency leads to dysbiosis of gut microbiota contributing to the depressive-like behaviors in mice","volume":"1819","author":"Liu","year":"2023","journal-title":"Brain Res."},{"key":"10.1016\/j.neubiorev.2026.106847_bib38","article-title":"The role of exercise-related FNDC5\/irisin in depression","volume":"15","author":"Liu","year":"2024","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.neubiorev.2026.106847_bib39","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/s41591-018-0275-4","article-title":"Exercise-linked FNDC5\/irisin rescues synaptic plasticity and memory defects in Alzheimer\u2019s models","volume":"25","author":"Lourenco","year":"2019","journal-title":"Nat. Med."},{"key":"10.1016\/j.neubiorev.2026.106847_bib40","doi-asserted-by":"crossref","DOI":"10.3389\/fncel.2022.953991","article-title":"Irisin stimulates protective signaling pathways in rat hippocampal neurons","volume":"16","author":"Lourenco","year":"2022","journal-title":"Front. Cell. Neurosci."},{"key":"10.1016\/j.neubiorev.2026.106847_bib41","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1210\/endrev\/bnab003","article-title":"Progress and challenges in the biology of FNDC5 and Irisin","volume":"42","author":"Maak","year":"2021","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.neubiorev.2026.106847_bib42","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1016\/j.celrep.2018.04.045","article-title":"GSK3\u03b2 regulates brain energy metabolism","volume":"23","author":"Martin","year":"2018","journal-title":"Cell. Rep."},{"key":"10.1016\/j.neubiorev.2026.106847_bib43","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-025-11389-w","article-title":"Emotional state in patients after COVID-19 in relation to comprehensive rehabilitation, Brain-Derived neurotrophic factor, Irisin levels, and selected clinical factors","volume":"15","author":"Mi\u0144ko","year":"2025","journal-title":"Sci. Rep."},{"key":"10.1016\/j.neubiorev.2026.106847_bib44","doi-asserted-by":"crossref","first-page":"554","DOI":"10.3390\/antiox14050554","article-title":"Role and functions of irisin: a perspective on recent developments and neurodegenerative diseases","volume":"14","author":"Minuti","year":"2025","journal-title":"Antioxidants"},{"key":"10.1016\/j.neubiorev.2026.106847_bib45","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/j.metabol.2013.04.007","article-title":"Pharmacological concentrations of irisin increase cell proliferation without influencing markers of neurite outgrowth and synaptogenesis in mouse H19-7 hippocampal cell lines","volume":"62","author":"Moon","year":"2013","journal-title":"Metabolism"},{"key":"10.1016\/j.neubiorev.2026.106847_bib46","doi-asserted-by":"crossref","first-page":"E769","DOI":"10.1210\/jc.2012-2749","article-title":"Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance","volume":"98","author":"Moreno-Navarrete","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.neubiorev.2026.106847_bib47","doi-asserted-by":"crossref","first-page":"244","DOI":"10.3390\/cells11020244","article-title":"Treadmill exercise prevents decline in spatial learning and memory in 3\u00d7Tg-AD mice through enhancement of structural synaptic plasticity of the hippocampus and prefrontal cortex","volume":"11","author":"Mu","year":"2022","journal-title":"Cells"},{"key":"10.1016\/j.neubiorev.2026.106847_bib48","doi-asserted-by":"crossref","DOI":"10.1016\/j.peptides.2025.171394","article-title":"Irisin prevents visceral hypersensitivity and colonic hyperpermeability in a rat model of irritable bowel syndrome","volume":"188","author":"Nozu","year":"2025","journal-title":"Peptides"},{"key":"10.1016\/j.neubiorev.2026.106847_bib49","doi-asserted-by":"crossref","first-page":"13480","DOI":"10.3390\/ijms252413480","article-title":"Irisin: a multifaceted hormone bridging exercise and disease pathophysiology","volume":"25","author":"Paoletti","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.neubiorev.2026.106847_bib50","article-title":"Mitochondria damaged by oxygen glucose deprivation can be restored through activation of the PI3K\/Akt pathway and inhibition of calcium influx by amlodipine camsylate","volume":"9","author":"Park","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.neubiorev.2026.106847_bib51","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1161\/STROKEAHA.125.053168","article-title":"Recombinant irisin therapy alters brain transcriptome and protects against ischemic damage in middle-aged rats","volume":"57","author":"Patel","year":"2026","journal-title":"Stroke"},{"key":"10.1016\/j.neubiorev.2026.106847_bib52","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/S0140-6736(18)31612-X","article-title":"The Lancet Commission on global mental health and sustainable development","volume":"392","author":"Patel","year":"2018","journal-title":"Lancet Lond. Engl."},{"key":"10.1016\/j.neubiorev.2026.106847_bib53","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.bbr.2017.09.033","article-title":"Insulin modulates hippocampally-mediated spatial working memory via glucose transporter-4","volume":"338","author":"Pearson-Leary","year":"2018","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.neubiorev.2026.106847_bib54","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/s41574-019-0174-x","article-title":"Physical activity and muscle-brain crosstalk","volume":"15","author":"Pedersen","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.neubiorev.2026.106847_bib55","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.molimm.2017.09.014","article-title":"Irisin protects against neuronal injury induced by oxygen-glucose deprivation in part depends on the inhibition of ROS-NLRP3 inflammatory signaling pathway","volume":"91","author":"Peng","year":"2017","journal-title":"Mol. Immunol."},{"key":"10.1016\/j.neubiorev.2026.106847_bib56","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/S0140-6736(21)00359-7","article-title":"Anxiety disorders","volume":"397","author":"Penninx","year":"2021","journal-title":"Lancet Lond. Engl."},{"key":"10.1016\/j.neubiorev.2026.106847_bib57","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.3390\/ijms22041605","article-title":"FNDC5\/Irisin System in Neuroinflammation and Neurodegenerative Diseases: Update and Novel Perspective","volume":"22","author":"Pignataro","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.neubiorev.2026.106847_bib58","doi-asserted-by":"crossref","first-page":"7596","DOI":"10.3390\/ijms23147596","article-title":"Antidepressant Effect of Intermittent Long-Term Systemic Administration of Irisin in Mice","volume":"23","author":"Pignataro","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.neubiorev.2026.106847_bib59","doi-asserted-by":"crossref","first-page":"6715","DOI":"10.3390\/ijms24076715","article-title":"Once-Daily Subcutaneous Irisin Administration Mitigates Depression- and Anxiety-like Behavior in Young Mice","volume":"24","author":"Pignataro","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.neubiorev.2026.106847_bib60","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1523\/JNEUROSCI.19-05-01541.1999","article-title":"Integrin subunit gene expression is regionally differentiated in adult brain","volume":"19","author":"Pinkstaff","year":"1999","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"10.1016\/j.neubiorev.2026.106847_bib61","doi-asserted-by":"crossref","first-page":"E512","DOI":"10.1152\/ajpendo.00308.2013","article-title":"The identification of irisin in human cerebrospinal fluid: influence of adiposity, metabolic markers, and gestational diabetes","volume":"306","author":"Piya","year":"2014","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"10.1016\/j.neubiorev.2026.106847_bib62","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.neuroscience.2022.07.018","article-title":"Irisin: A promising treatment for neurodegenerative diseases","volume":"498","author":"Qi","year":"2022","journal-title":"Neuroscience"},{"key":"10.1016\/j.neubiorev.2026.106847_bib63","doi-asserted-by":"crossref","DOI":"10.1016\/j.arr.2025.102687","article-title":"Neurobiological role and therapeutic potential of exercise-induced irisin in Alzheimer\u2019s disease management","volume":"105","author":"Ratne","year":"2025","journal-title":"Ageing Res. Rev."},{"key":"10.1016\/j.neubiorev.2026.106847_bib64","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2023.122393","article-title":"Irisin: An unveiled bridge between physical exercise and a healthy brain","volume":"339","author":"Sadier","year":"2024","journal-title":"Life Sci."},{"key":"10.1016\/j.neubiorev.2026.106847_bib65","doi-asserted-by":"crossref","first-page":"33738","DOI":"10.1074\/jbc.M113.516641","article-title":"The structure of irisin reveals a novel intersubunit \u03b2-sheet fibronectin type III (FNIII) dimer: implications for receptor activation","volume":"288","author":"Schumacher","year":"2013","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.neubiorev.2026.106847_bib66","doi-asserted-by":"crossref","DOI":"10.1016\/j.expneurol.2019.113043","article-title":"Physical exercise ameliorates psychiatric disorders and cognitive dysfunctions by hippocampal mitochondrial function and neuroplasticity in post-traumatic stress disorder","volume":"322","author":"Seo","year":"2019","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.neubiorev.2026.106847_bib67","doi-asserted-by":"crossref","first-page":"e751","DOI":"10.1093\/nutrit\/nuae076","article-title":"Effect of saffron versus selective serotonin reuptake inhibitors (SSRIs) in treatment of depression and anxiety: a meta-analysis of randomized controlled trials","volume":"83","author":"Shafiee","year":"2025","journal-title":"Nutr. Rev."},{"key":"10.1016\/j.neubiorev.2026.106847_bib68","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1016\/j.drudis.2022.03.019","article-title":"The role of irisin in metabolic flexibility: beyond adipose tissue browning","volume":"27","author":"Shen","year":"2022","journal-title":"Drug. Discov. Today"},{"key":"10.1016\/j.neubiorev.2026.106847_bib69","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.pnpbp.2018.03.004","article-title":"Central irisin administration affords antidepressant-like effect and modulates neuroplasticity-related genes in the hippocampus and prefrontal cortex of mice","volume":"84","author":"Siteneski","year":"2018","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"10.1016\/j.neubiorev.2026.106847_bib70","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/S0140-6736(18)31793-8","article-title":"Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis","volume":"393","author":"Slee","year":"2019","journal-title":"Lancet"},{"key":"10.1016\/j.neubiorev.2026.106847_bib71","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s12993-025-00275-0","article-title":"Acute high-intensity noise exposure exacerbates anxiety-like behavior via neuroinflammation and blood brain barrier disruption of hippocampus in male rats","volume":"21","author":"Song","year":"2025","journal-title":"Behav. Brain Funct. BBF"},{"key":"10.1016\/j.neubiorev.2026.106847_bib72","doi-asserted-by":"crossref","first-page":"6379","DOI":"10.1073\/pnas.1817391116","article-title":"Insulin signaling in the hippocampus and amygdala regulates metabolism and neurobehavior","volume":"116","author":"Soto","year":"2019","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.neubiorev.2026.106847_bib73","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1152\/japplphysiol.00343.2011","article-title":"Exercise training increases mitochondrial biogenesis in the brain","volume":"111","author":"Steiner","year":"2011","journal-title":"J. Appl. Physiol."},{"key":"10.1016\/j.neubiorev.2026.106847_bib74","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1136\/gutjnl-2017-314759","article-title":"Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression","volume":"67","author":"Stevens","year":"2018","journal-title":"Gut"},{"key":"10.1016\/j.neubiorev.2026.106847_bib75","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jpsychires.2025.11.027","article-title":"Targeting exercise triggered irisin for therapeutic intervention of autism-associated social anxiety","volume":"193","author":"Tatode","year":"2026","journal-title":"J. Psychiatr. Res."},{"key":"10.1016\/j.neubiorev.2026.106847_bib76","doi-asserted-by":"crossref","first-page":"7671","DOI":"10.1074\/jbc.M114.617399","article-title":"SMAD3 negatively regulates serum irisin and skeletal muscle FNDC5 and peroxisome proliferator-activated receptor \u03b3 coactivator 1-\u03b1 (PGC-1\u03b1) during exercise","volume":"290","author":"Tiano","year":"2015","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.neubiorev.2026.106847_bib77","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.15252\/embr.201642951","article-title":"The economic costs of mental disorders: Do our societies react appropriately to the burden of mental disorders?","volume":"17","author":"Trautmann","year":"2016","journal-title":"EMBO Rep."},{"key":"10.1016\/j.neubiorev.2026.106847_bib78","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.freeradbiomed.2023.03.014","article-title":"Irisin drives macrophage anti-inflammatory differentiation via JAK2-STAT6-dependent activation of PPAR\u03b3 and Nrf2 signaling","volume":"201","author":"Tu","year":"2023","journal-title":"Free. Radic. Biol. Med."},{"key":"10.1016\/j.neubiorev.2026.106847_bib79","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.neulet.2018.04.023","article-title":"Regular aerobic exercise correlates with reduced anxiety and increased levels of irisin in brain and white adipose tissue","volume":"676","author":"Uysal","year":"2018","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.neubiorev.2026.106847_bib80","doi-asserted-by":"crossref","DOI":"10.1038\/srep29898","article-title":"FNDC5 expression and circulating irisin levels are modified by diet and hormonal conditions in hypothalamus, adipose tissue and muscle","volume":"6","author":"Varela-Rodr\u00edguez","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.neubiorev.2026.106847_bib81","doi-asserted-by":"crossref","DOI":"10.1016\/j.exger.2024.112640","article-title":"Effects of physical exercise on Irisin and BDNF concentrations, and their relationship with cardiometabolic and mental health of individuals with metabolic syndrome: a systematic review","volume":"198","author":"Villamil-Parra","year":"2024","journal-title":"Exp. Gerontol."},{"key":"10.1016\/j.neubiorev.2026.106847_bib82","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1530\/JOE-18-0574","article-title":"Irisin in the primate hypothalamus and its effect on GnRH in vitro","volume":"241","author":"Wahab","year":"2019","journal-title":"J. Endocrinol."},{"key":"10.1016\/j.neubiorev.2026.106847_bib83","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.bbi.2024.12.019","article-title":"Irisin reprograms microglia through activation of STAT6 and prevents cognitive dysfunction after surgery in mice","volume":"125","author":"Wang","year":"2025","journal-title":"Brain. Behav. Immun."},{"key":"10.1016\/j.neubiorev.2026.106847_bib84","doi-asserted-by":"crossref","DOI":"10.1155\/2018\/9070341","article-title":"Irisin Exerts Neuroprotective Effects on Cultured Neurons by Regulating Astrocytes","volume":"2018","author":"Wang","year":"2018","journal-title":"Mediat. Inflamm."},{"key":"10.1016\/j.neubiorev.2026.106847_bib85","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/1567179","article-title":"Irisin Attenuates neuroinflammation and prevents the memory and cognitive deterioration in streptozotocin-induced diabetic mice","volume":"2019","author":"Wang","year":"2019","journal-title":"Mediat. Inflamm."},{"key":"10.1016\/j.neubiorev.2026.106847_bib86","doi-asserted-by":"crossref","DOI":"10.14814\/phy2.14323","article-title":"Effect of exercise training on the FNDC5\/BDNF pathway in spontaneously hypertensive rats","volume":"7","author":"Wang","year":"2019","journal-title":"Physiol. Rep."},{"key":"10.1016\/j.neubiorev.2026.106847_bib87","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s12974-022-02438-6","article-title":"Irisin ameliorates neuroinflammation and neuronal apoptosis through integrin \u03b1V\u03b25\/AMPK signaling pathway after intracerebral hemorrhage in mice","volume":"19","author":"Wang","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"10.1016\/j.neubiorev.2026.106847_bib88","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1186\/s12891-025-08622-y","article-title":"Irisin mitigates osteoporotic-associated bone loss and gut dysbiosis in ovariectomized mice by modulating microbiota, metabolites, and intestinal barrier integrity","volume":"26","author":"Wang","year":"2025","journal-title":"BMC Musculoskelet. Disord."},{"key":"10.1016\/j.neubiorev.2026.106847_bib89","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/1742-2094-8-157","article-title":"Microglia use multiple mechanisms to mediate interactions with vitronectin; non-essential roles for the highly-expressed \u03b1v\u03b23 and \u03b1v\u03b25 integrins","volume":"8","author":"Welser-Alves","year":"2011","journal-title":"J. Neuroinflamm."},{"key":"10.1016\/j.neubiorev.2026.106847_bib90","series-title":"Depression and Other Common Mental Disorders [WWW Document]","article-title":"URL","author":"World Health Organization","year":"2017"},{"key":"10.1016\/j.neubiorev.2026.106847_bib91","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.cmet.2013.09.008","article-title":"Exercise induces hippocampal BDNF through a PGC-1\u03b1\/FNDC5 pathway","volume":"18","author":"Wrann","year":"2013","journal-title":"Cell. Metab."},{"key":"10.1016\/j.neubiorev.2026.106847_bib92","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1186\/s12951-026-04109-7","article-title":"T7 peptide-engineered liposomal Irisin mitigates PND progression through AMPK\/PGC-1\u03b1 signaling: multi-omic evidence of metabolic and epigenetic modulation","volume":"24","author":"Wu","year":"2026","journal-title":"J. Nanobiotechnology"},{"key":"10.1016\/j.neubiorev.2026.106847_bib93","doi-asserted-by":"crossref","DOI":"10.1155\/2021\/2630445","article-title":"Curcumin Relieves Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior through the PGC-1\u03b1\/FNDC5\/BDNF Pathway","volume":"2021","author":"Wu","year":"2021","journal-title":"Behav. Neurol."},{"key":"10.1016\/j.neubiorev.2026.106847_bib94","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s12974-025-03493-5","article-title":"Exercise-induced irisin ameliorates cognitive impairment following chronic cerebral hypoperfusion by suppressing neuroinflammation and hippocampal neuronal apoptosis","volume":"22","author":"Xiao","year":"2025","journal-title":"J. Neuroinflamm."},{"key":"10.1016\/j.neubiorev.2026.106847_bib95","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.ibneur.2024.08.009","article-title":"Irisin alleviates chronic constriction injury-induced hyperalgesia and affective disorders in mice through NF-\u03baB and Nrf2 signaling pathways","volume":"17","author":"Xie","year":"2024","journal-title":"IBRO Neurosci. Rep."},{"key":"10.1016\/j.neubiorev.2026.106847_bib96","doi-asserted-by":"crossref","DOI":"10.1016\/j.npep.2025.102537","article-title":"Irisin alleviates anxiety and deficits in fear extinction in PTSD within SPS mouse model","volume":"113","author":"Xie","year":"2025","journal-title":"Neuropeptides"},{"key":"10.1016\/j.neubiorev.2026.106847_bib97","doi-asserted-by":"crossref","DOI":"10.1016\/j.peptides.2025.171349","article-title":"Effects of irisin on ovariectomy-induced depression, anxiety, and bodyweight growth in female mice","volume":"184","author":"Xie","year":"2025","journal-title":"Peptides"},{"key":"10.1016\/j.neubiorev.2026.106847_bib98","doi-asserted-by":"crossref","DOI":"10.1002\/alz70859_105359","article-title":"A\u03b212-28P administration alleviates anxiety in an Alzheimer\u2019s disease mouse model","volume":"21","author":"Yang","year":"2025","journal-title":"Alzheimers Dement."},{"key":"10.1016\/j.neubiorev.2026.106847_bib99","article-title":"FNDC5\/irisin mediates the protective effects of Innovative theta-shaking exercise on mouse memory","volume":"10","author":"Yao","year":"2024","journal-title":"Heliyon"},{"key":"10.1016\/j.neubiorev.2026.106847_bib100","doi-asserted-by":"crossref","DOI":"10.1016\/j.neulet.2023.137245","article-title":"Effects of chronic irisin treatment on brain monoamine levels in the hypothalamic and subcortical nuclei of adult male and female rats: An HPLC-ECD study","volume":"806","author":"Yardimci","year":"2023","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.neubiorev.2026.106847_bib101","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/s44321-024-00179-y","article-title":"Microbial metabolites tune amygdala neuronal hyperexcitability and anxiety-linked behaviors","volume":"17","author":"Yu","year":"2025","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.neubiorev.2026.106847_bib102","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.1007\/s00213-018-5041-2","article-title":"PGC-1\u03b1-FNDC5-BDNF signaling pathway in skeletal muscle confers resilience to stress in mice subjected to chronic social defeat","volume":"235","author":"Zhan","year":"2018","journal-title":"Psychopharmacol. (Berl. )"},{"key":"10.1016\/j.neubiorev.2026.106847_bib103","article-title":"Irisin restrains neuroinflammation in mouse experimental autoimmune encephalomyelitis via regulating microglia activation","volume":"16","author":"Zhang","year":"2025","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.neubiorev.2026.106847_bib104","doi-asserted-by":"crossref","first-page":"514","DOI":"10.2337\/db13-1106","article-title":"Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling","volume":"63","author":"Zhang","year":"2014","journal-title":"Diabetes"},{"key":"10.1016\/j.neubiorev.2026.106847_bib105","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1038\/s42003-025-09000-z","article-title":"Engineered long-acting Irisin-albumin binding domain fusion protein for enhanced anti-inflammatory efficacy in lipopolysaccharide-induced systemic inflammation","volume":"8","author":"Zhu","year":"2025","journal-title":"Commun. Biol."},{"key":"10.1016\/j.neubiorev.2026.106847_bib106","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2025.114201","article-title":"Irisin promotes autophagy and attenuates NLRP3 inflammasome activation in Parkinson\u2019s disease","volume":"149","author":"Zhu","year":"2025","journal-title":"Int. Immunopharmacol."}],"container-title":["Neuroscience &amp; Biobehavioral Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0149763426003040?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0149763426003040?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:25:31Z","timestamp":1786541131000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0149763426003040"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":106,"alternative-id":["S0149763426003040"],"URL":"https:\/\/doi.org\/10.1016\/j.neubiorev.2026.106847","relation":{},"ISSN":["0149-7634"],"issn-type":[{"value":"0149-7634","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Irisin and anxiety-like behaviors: Mechanistic integration of peripheral\u2013central crosstalk, neuroinflammation, and neural plasticity","name":"articletitle","label":"Article Title"},{"value":"Neuroscience & Biobehavioral Reviews","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.neubiorev.2026.106847","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"106847"}}