Imaging Brain Networks After Cancer and Chemotherapy

Nudelman, Kelly; McDonald, Brenna C.; Saykin, Andrew J.

doi:10.1001/jamaoncol.2015.4551

Cited by 1 publication

(2 citation statements)

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“…Reduced hippocampal volume has been observed in human neuroimaging studies of both cancer-related cognitive decline and Alzheimer's disease (Nudelman et al 2016;Saykin et al 2013;Schuff et al 2009). In this study, we compared the hippocampus of APOE3 and APOE4 mice, both in the absence and in the presence of doxorubicin treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Human and animal studies suggest that cancer chemotherapeutic agents can lead to alterations in biomarkers of aging (Sanoff et al 2014), cause cognitive decline (Kesler and Blayney 2016;Sanoff et al 2014), and result in brain atrophy that mimics degenerative agerelated changes (Kesler and Blayney 2016;Mandelblatt et al 2013;Mandelblatt et al 2014b;Nudelman et al 2016). Hence, older cancer survivors are likely to be particularly vulnerable to experiencing cognitive decline as a result of age and cancer and its treatments.…”

Section: Introductionmentioning

confidence: 99%

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Development of a Human APOE Knock-in Mouse Model for Study of Cognitive Function After Cancer Chemotherapy

et al. 2018

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Cancer-related cognitive impairment in breast cancer patients exposed to multi-agent chemotherapy regimens is associated with the Apolipoprotein E4 (APOE4) allele. However, it is difficult to determine the effects of specific agents on cognitive impairment in human studies. We describe the development of a human APOE knock-in congenic C57BL/6J mouse model to study cancer-related cognitive impairment. Female APOE3 and APOE4 homozygous mice were either left untreated or treated with the most commonly used breast cancer therapeutic agent, doxorubicin. APOE3 and APOE4 mice had similar behaviors in exploratory and anxiety assays, which were affected transiently by doxorubicin treatment. Spatial learning and memory were measured in a Barnes Maze: after four days of training, control APOE3 and APOE4 mice were able to escape with similar latencies. In contrast, doxorubicin-treated APOE4 mice had markedly impaired learning compared to doxorubicin-treated APOE3 mice at all time points. Voxel based morphometry of magnetic resonance images revealed that doxorubicin treatment caused significant changes in the cortex and hippocampus of in both APOE3 and APOE4 mouse brains, but the differences were significantly greater in the APOE4 brains. The results indicate that doxorubicin-exposed APOE4 mice recapitulate key aspects of human cancer-related cognitive impairment. These data support the usefulness of this novel pre-clinical model for future elucidation of the genetic and molecular interactions of APOE genotype with chemotherapy; this model can also allow extension to prospective studies of older mice to study these interactions in the context of aging.

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Section: Discussionmentioning

confidence: 99%