{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T22:04:10Z","timestamp":1787695450334,"version":"build-2784847793"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82401427"],"award-info":[{"award-number":["82401427"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870861"],"award-info":[{"award-number":["81870861"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Behav. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Brain dysfunction is a common post-chemotherapy sequela in acute lymphoblastic leukemia (ALL) survivors and is associated with poor academic performance and reduced work ability. The prevention of brain dysfunction in ALL survivors remains a clinical challenge. In this study, we evaluated the preventive effects of probiotics on chemotherapy-induced brain development damage in a preclinical setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The clinical ALL chemotherapy setting was mimicked by intraperitoneally injecting doxorubicin into 4-week-old mice once every 3\u202fdays for 2\u202fweeks. Probiotics were administered in the drinking water from the beginning of chemotherapy until adulthood. Behaviors at adulthood were assessed using open field, elevated plus maze, novel object recognition, and Barnes maze tests. Fecal microbiota composition was analyzed using 16S ribosomal RNA (rRNA) gene sequence. Hippocampal neurogenesis was assessed using EdU staining and DCX immunostaining. Synaptic protein expressions were detected using Western blotting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Early-life chemotherapy induced cognitive dysfunction in adulthood, as demonstrated by impairments in the novel object recognition and Barnes maze tests, but it did not significantly alter anxiety-like behavior in the elevated plus maze. Early-life chemotherapy also induced fecal microbiota dysbiosis both at the end of chemotherapy and in adulthood. Probiotic supplementation alleviated early-life chemotherapy-induced cognitive dysfunction and fecal microbiota dysbiosis in adulthood. In addition, probiotic supplementation also alleviated early-life chemotherapy-induced hippocampal neurogenesis impairments and synaptic protein loss.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Probiotic supplementation can improve early-life chemotherapy-induced brain development impairments in mice by modulating hippocampal neurogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnbeh.2025.1697727","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T06:35:13Z","timestamp":1765953313000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Probiotic supplementation attenuated early-life chemotherapy-induced brain development impairment in mice"],"prefix":"10.3389","volume":"19","author":[{"given":"Aihua","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbin","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e151025","DOI":"10.1001\/jamapediatrics.2015.1025","article-title":"Breastfeeding and childhood leukemia incidence: a meta-analysis and systematic review","volume":"169","author":"Amitay","year":"2015","journal-title":"JAMA Pediatr."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"49","DOI":"10.3389\/fnins.2018.00049","article-title":"The vagus nerve at the Interface of the microbiota-gut-brain axis","volume":"12","author":"Bonaz","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.bbi.2024.06.005","article-title":"Microbial reconstitution reverses prenatal stress-induced cognitive impairment and synaptic deficits in rat offspring","volume":"120","author":"Chen","year":"2024","journal-title":"Brain Behav. Immun."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/j.lfs.2013.08.011","article-title":"A randomized trial of cognitive rehabilitation in cancer survivors","volume":"93","author":"Cherrier","year":"2013","journal-title":"Life Sci."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e456","DOI":"10.1016\/S2352-3026(16)30110-7","article-title":"Leukoencephalopathy and long-term neurobehavioural, neurocognitive, and brain imaging outcomes in survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy: a longitudinal analysis","volume":"3","author":"Cheung","year":"2016","journal-title":"Lancet Haematol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1002\/kjm2.12061","article-title":"A cross-sectional follow-up study of physical morbidities, neurocognitive function, and attention problems in post-treatment childhood acute lymphoblastic leukemia survivors","volume":"35","author":"Chiou","year":"2019","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"199","DOI":"10.3390\/nu13010199","article-title":"Nutritional support of neurodevelopment and cognitive function in infants and young children-an update and novel insights","volume":"13","author":"Cohen Kadosh","year":"2021","journal-title":"Nutrients"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"3894","DOI":"10.1200\/JCO.2015.61.6672","article-title":"Computerized cognitive training for amelioration of cognitive late effects among childhood cancer survivors: a randomized controlled trial","volume":"33","author":"Conklin","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1152\/physrev.00018.2018","article-title":"The microbiota-gut-brain axis","volume":"99","author":"Cryan","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"3418","DOI":"10.1200\/JCO.20.00493","article-title":"Reduced morbidity and mortality in survivors of childhood acute lymphoblastic leukemia: a report from the childhood cancer survivor study","volume":"38","author":"Dixon","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2520","DOI":"10.1002\/cncr.34209","article-title":"Mindfulness-based stress reduction and cognitive function among breast cancer survivors: a randomized controlled trial","volume":"128","author":"Duval","year":"2022","journal-title":"Cancer"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1093\/jnci\/djy089","article-title":"Brain activity associated with attention deficits following chemotherapy for childhood acute lymphoblastic leukemia","volume":"111","author":"Fellah","year":"2019","journal-title":"J. Natl. Cancer Inst."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e071726","DOI":"10.1136\/bmj-2022-071726","article-title":"Cognitive impairment after cancer treatment: mechanisms, clinical characterization, and management","volume":"380","author":"Fleming","year":"2023","journal-title":"BMJ"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.bbi.2021.01.021","article-title":"Neuroimmune reactivity marker expression in rodent models of chemotherapy-induced cognitive impairment: a systematic scoping review","volume":"94","author":"George","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1856","DOI":"10.1002\/pon.3222","article-title":"Working memory training in survivors of pediatric cancer: a randomized pilot study","volume":"22","author":"Hardy","year":"2013","journal-title":"Psychooncology"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1177\/1534735415617021","article-title":"YOCAS\u00a9\u00ae yoga reduces self-reported memory difficulty in cancer survivors in a nationwide randomized clinical trial: investigating relationships between memory and sleep","volume":"15","author":"Janelsins","year":"2016","journal-title":"Integr. Cancer Ther."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.ejca.2021.11.006","article-title":"Probiotic supplement attenuates chemotherapy-related cognitive impairment in patients with breast cancer: a randomised, double-blind, and placebo-controlled trial","volume":"161","author":"Juan","year":"2022","journal-title":"Eur. J. Cancer"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"2644","DOI":"10.1200\/JCO.2015.65.4574","article-title":"Chemotherapy pharmacodynamics and neuroimaging and neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia","volume":"34","author":"Krull","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"2181","DOI":"10.1200\/JCO.2017.76.4696","article-title":"Neurocognitive outcomes and interventions in long-term survivors of childhood cancer","volume":"36","author":"Krull","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1038\/nrclinonc.2013.195","article-title":"Treatment-related cardiotoxicity in survivors of childhood cancer","volume":"10","author":"Lipshultz","year":"2013","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1007\/s11764-018-0679-7","article-title":"Evolution of neurocognitive function in long-term survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only","volume":"12","author":"Liu","year":"2018","journal-title":"J. Cancer Surviv."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"eadf8977","DOI":"10.1126\/scitranslmed.adf8977","article-title":"Targeting ryanodine receptor type 2 to mitigate chemotherapy-induced neurocognitive impairments in mice","volume":"15","author":"Liu","year":"2023","journal-title":"Sci. Transl. Med."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/s41392-024-01743-1","article-title":"Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases","volume":"9","author":"Loh","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1016\/S0140-6736(19)33018-1","article-title":"Acute lymphoblastic leukaemia","volume":"395","author":"Malard","year":"2020","journal-title":"Lancet"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1053\/j.gastro.2020.10.066","article-title":"The microbiota-gut-brain axis: from motility to mood","volume":"160","author":"Margolis","year":"2021","journal-title":"Gastroenterology"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"101205","DOI":"10.1016\/j.mam.2023.101205","article-title":"Doxorubicin and other anthracyclines in cancers: activity, chemoresistance and its overcoming","volume":"93","author":"Mattioli","year":"2023","journal-title":"Mol. Asp. Med."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1053\/j.gastro.2016.07.044","article-title":"The effect of microbiota and the immune system on the development and organization of the enteric nervous system","volume":"151","author":"Obata","year":"2016","journal-title":"Gastroenterology"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1007\/s40264-022-01182-3","article-title":"Chemobrain in breast cancer: mechanisms, clinical manifestations, and potential interventions","volume":"45","author":"Onzi","year":"2022","journal-title":"Drug Saf."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1126\/science.abl5163","article-title":"Impact of neurodegenerative diseases on human adult hippocampal neurogenesis","volume":"374","author":"Terreros-Roncal","year":"2021","journal-title":"Science"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"CD011325","DOI":"10.1002\/14651858.CD011325.pub2","article-title":"Non-pharmacological interventions for cognitive impairment due to systemic cancer treatment","volume":"2022","author":"Treanor","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1080\/09297049.2017.1386170","article-title":"Characterizing neurocognitive late effects in childhood leukemia survivors using a combination of neuropsychological and cognitive neuroscience measures","volume":"24","author":"van der Plas","year":"2018","journal-title":"Child Neuropsychol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1705","DOI":"10.1200\/JCO.20.02322","article-title":"Cognitive impairment in survivors of pediatric acute lymphoblastic leukemia treated with chemotherapy only","volume":"39","author":"van der Plas","year":"","journal-title":"J. Clin. Oncol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1038\/s41390-020-01230-7","article-title":"Cognitive and behavioral risk factors for low quality of life in survivors of childhood acute lymphoblastic leukemia","volume":"90","author":"van der Plas","year":"","journal-title":"Pediatr. Res."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1007\/s13311-019-00806-4","article-title":"Subcutaneous administration of \u03b2-hydroxybutyrate improves learning and memory of sepsis surviving mice","volume":"17","author":"Wang","year":"2020","journal-title":"Neurotherapeutics"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1093\/procel\/pwad026","article-title":"The microbiota-gut-brain axis and neurodevelopmental disorders","volume":"14","author":"Wang","year":"2023","journal-title":"Protein Cell"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"123","DOI":"10.3322\/caac.21258","article-title":"Clinical characteristics, pathophysiology, and management of noncentral nervous system cancer-related cognitive impairment in adults","volume":"65","author":"Wefel","year":"2015","journal-title":"CA Cancer J. Clin."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1097\/PHM.0000000000002531","article-title":"Comparative effects of exercise interventions and mindfulness-based interventions for cognitive impairment and quality of life in breast cancer survivors during or after cancer treatment: a systematic review and Bayesian network meta-analysis","volume":"103","author":"Zeng","year":"2024","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"eabb9888","DOI":"10.1126\/sciadv.abb9888","article-title":"IL4-driven microglia modulate stress resilience through BDNF-dependent neurogenesis","volume":"7","author":"Zhang","year":"2021","journal-title":"Sci. Adv."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"888726","DOI":"10.3389\/fphar.2022.888726","article-title":"Schisandrin alleviates the cognitive impairment in rats with Alzheimer\u2019s disease by altering the gut microbiota composition to modulate the levels of endogenous metabolites in the plasma, brain, and feces","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1038\/s41420-023-01424-y","article-title":"Blocking the CXCL1-CXCR2 axis enhances the effects of doxorubicin in HCC by remodelling the tumour microenvironment via the NF-\u03baB\/IL-1\u03b2\/CXCL1 signalling pathway","volume":"9","author":"Zhao","year":"2023","journal-title":"Cell Death Discov."}],"container-title":["Frontiers in Behavioral Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnbeh.2025.1697727\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T06:35:17Z","timestamp":1765953317000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnbeh.2025.1697727\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,17]]},"references-count":41,"alternative-id":["10.3389\/fnbeh.2025.1697727"],"URL":"https:\/\/doi.org\/10.3389\/fnbeh.2025.1697727","relation":{},"ISSN":["1662-5153"],"issn-type":[{"value":"1662-5153","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,17]]},"article-number":"1697727"}}