Development of a mouse model to study the long-term effects of chemotherapy on brain function

Simple item page
dc.creatorTrinh, Oanhen_US
dc.creatorVann, Philipen_US
dc.creatorDavis, Delaneyen_US
dc.creatorLuedtke, Robert R.en_US
dc.creatorBasha, Riyazen_US
dc.creatorSingh, Meharvanen_US
dc.creatorSumien, Nathalieen_US
dc.date.accessioned2023-04-05T13:31:14Z
dc.date.available2023-04-05T13:31:14Z
dc.date.issued2023en_US
dc.descriptionResearch Appreciation Day Award Winner - School of Biomedical Sciences, 2023 Department of Pharmacology & Neuroscience Award - 1st Placeen_US
dc.description.abstractPurpose: While remaining an effective life-saving intervention for cancer patients, chemotherapy has been associated with many neurotoxic side effects, including chemotherapy-related cognitive impairments (CRCI). Chemotherapy exposure leads to a decline in learning, memory, processing speed, attention, and executive functions, which may persist for more than 20 years post-treatment, impairing the quality of daily lives of survivors. Childhood cancer survivors are particularly vulnerable to chemotherapy and have been impacted in their educational achievements, employment, social relationships, and even life expectancy. Most common childhood cancers are often treated with the folate-inhibitor methotrexate (MTX). Our study aimed at establishing a tumor-free mouse model of MTX-induced brain impairments. We hypothesized that early exposure to MTX would induce impairment in cognition, as well as motor and affective functions. Methods: Male and female C57BL6/J postnatal day 15 pups received intraperitoneal injections of saline or MTX (2 mg/kg) once a day for 3 days. Pups were weaned on PND21, and subsets were behaviorally characterized at 1 or 7 months after MTX exposure (n=6-8 for 1.5 months old, and n=11-13 for 8 months old) for motor, affective and cognitive functions using a comprehensive behavioral test battery. Results: At 1.5 months, coordination and motor learning was significantly impaired in males and improved in females. All other measures did not reveal any other significant effects, however trends of impaired motor and cognitive functions could be discerned. At 8 months, there were no effects of MTX on motor, affective and some cognitive functions. However, MTX exposure led to an impairment on spatial learning and memory and increased swimming speed. Conclusions: Studies at 1.5 months will need to be repeated to increase power and ascertain conclusions on brain functions. Early exposure to MTX treatment led to long-term impairments in both male and female mice and could be used as a model to test interventions to limit CRCI.en_US
dc.description.sponsorshipThe Feddersen Foundation. The Cancer Prevention and Research Institute of Texas (CPRIT).en_US
dc.identifier.urihttps://hdl.handle.net/20.500.12503/32243
dc.language.isoen
dc.titleDevelopment of a mouse model to study the long-term effects of chemotherapy on brain functionen_US
dc.typeposteren_US
dc.type.materialtexten_US

Files

Collections

Neuroscience