دورية أكاديمية
Translationally relevant mouse model of early life cancer and chemotherapy exposure results in brain and small intestine cytokine responses: A potential link to cognitive deficits
| العنوان: | Translationally relevant mouse model of early life cancer and chemotherapy exposure results in brain and small intestine cytokine responses: A potential link to cognitive deficits |
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| المؤلفون: | Konsman, Jan, Laaker, Collin, Lloyd, Kelsey, Hiltz, Adam, Smith, Brittany, Smail, Marissa, Reyes, Teresa |
| المساهمون: | Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), University of Cincinnati (UC) |
| المصدر: | ISSN: 0889-1591. |
| بيانات النشر: | HAL CCSD Elsevier |
| سنة النشر: | 2022 |
| المجموعة: | Archive ouverte HAL (Hyper Article en Ligne, CCSD - Centre pour la Communication Scientifique Directe) |
| مصطلحات موضوعية: | chemotherapy, executive function, small intestine inflammation, prefrontal cortex, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology |
| الوصف: | International audience ; Survivors of acute lymphoblastic leukemia (ALL), the most common childhood cancer, are at increased risk for long-term cognitive problems, including executive function deficits. The chemotherapeutic agent methotrexate (MTX) is used to treat most ALL patients, and is closely associated with cognitive deficits. To address how early life cancer chemotherapy leads to cognitive deficits, we developed a translationally relevant mouse model of leukemia survival that exposed mice to leukemic cells and chemotherapeutic drugs (vincristine and MTX, with leucovorin rescue) in early life. Male and female mice were tested several weeks later using novel object recognition (recognition memory) and 5-choice serial reaction time task (executive function). Gene expression of proinflammatory, white matter and synapseassociated molecules was assessed in the prefrontal cortex and small intestine both acutely after chemotherapy and chronically after cognitive testing. Early life cancer-chemotherapy exposure resulted in recognition memory and executive function deficits in adult male mice. Prefrontal cortex expression of the chemokine Ccl2 was increased acutely, while small intestine expression of the proinflammatory cytokine tumor necrosis factor-alpha was elevated both acutely (both sexes) and chronically (males only). Inflammation in the small intestine was correlated with prefrontal cortical proinflammatory and synaptic gene expression changes, as well as to executive function deficits. Collectively, these data indicate that the current protocol results in a robust mouse model in which to study cognitive deficits in leukemia survivors, and suggest that small intestine inflammation may represent a novel contributor to adverse CNS consequences of early life chemotherapy. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | hal-03836102; https://hal.science/hal-03836102Test; https://hal.science/hal-03836102/documentTest; https://hal.science/hal-03836102/file/Konsmanetal_BrainBehavImmun2022_HAL.pdfTest |
| DOI: | 10.1016/j.bbi.2021.10.003 |
| الإتاحة: | https://doi.org/10.1016/j.bbi.2021.10.003Test https://hal.science/hal-03836102Test https://hal.science/hal-03836102/documentTest https://hal.science/hal-03836102/file/Konsmanetal_BrainBehavImmun2022_HAL.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.1E1120FF |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.bbi.2021.10.003 |
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