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ORIGINAL RESEARCH article

Front. Behav. Neurosci.

Sec. Learning and Memory

Probiotic supplement attenuated the early life chemotherapy-induced brain development impairment in mice

Provisionally accepted
  • 1Third Xiangya Hospital, Central South University, Changsha, China
  • 2Tangshan People's Hospital, Tangshan, China

The final, formatted version of the article will be published soon.

Background: Brain dysfunction is a common post-chemotherapy sequelae in acute lymphoblastic leukemia(ALL)survivors and is associated with poor academic performance and work ability. The prevention of brain dysfunction in ALL survivors remains a clinical challenge. Here, we tested the preventive effects of probiotics on chemotherapy-induced brain development damage in pre-clinical setting. Methods: The clinical ALL chemotherapy setting was mimicked via intraperitoneally injecting doxorubicin into 4-week-old mice once every 3 days for 2 weeks. Probiotics were supplemented via drinking water from the beginning of chemotherapy to adulthood. The behaviors at adulthood were tested in Open field, Elevated plus maze, Novel object recognition, and Barnes maze. Fecal microbiota was detected with 16S ribosomal RNA (rRNA) gene sequence. Hippocampal neurogenesis was assessed via EdU staining and DCX immunostaining. Synaptic protein expressions were detected with western blotting. Results: Early life chemotherapy induced cognitive dysfunction in Novel object recognition and Barnes maze in adulthood, but did not significantly alter anxiety-like behavior at Elevated plus maze. Early life chemotherapy also induced fecal microbiota dysbiosis at the end of chemotherapy and the adulthood. Probiotics supplement alleviated early life chemotherapy induced cognitive dysfunction and fecal microbiota dysbiosis at adulthood. In addition, probiotics supplement also alleviated early life chemotherapy induced hippocampal neurogenesis impairment and synaptic protein loss. Conclusions: Probiotics supplement can improve early life chemotherapy-induced brain development impairment in mice via modulating hippocampal neurogenesis.

Keywords: early life chemotherapy, cognitive impairment, Probiotics, Acute Lymphoblastic Leukemia, Anxiety

Received: 02 Sep 2025; Accepted: 25 Nov 2025.

Copyright: © 2025 Tan, Chen, Juan, Tong and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Jianbin Tong
Zhibin Jiang

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