Research Paper Volume 9, Issue 7 pp 1660—1676
Chemo brain or tumor brain - that is the question: the presence of extracranial tumors profoundly affects molecular processes in the prefrontal cortex of TumorGraft mice
- 1 Department of Neuroscience, University of Lethbridge, Lethbridge, AB T1K 6T5, Canada
- 2 Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 6T5, Canada
- 3 Division of Biochemical Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079, USA
- 4 Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
- 5 Department of Oncology, Champions Oncology, Baltimore, MD 21205, USA
- 6 Leaders in Medicine Program, Cumming School of Medicine, University of Calgary, Calgary, T2N 1N4, Canada
received: April 11, 2017 ; accepted: May 22, 2017 ; published: July 29, 2017 ;https://doi.org/10.18632/aging.101243
How to Cite
Copyright: Kovalchuk et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Cancer chemotherapy causes numerous persistent central nervous system complications. This condition is known as chemo brain. Cognitive impairments occur even before treatment, and hence are referred to as cancer associated cognitive changes, or tumor brain. There is much yet to be learned about the mechanisms of both chemo brain and tumor brain. The frequency and timing of chemo brain and tumor brain occurrence and persistence strongly suggest they may be epigenetic in nature and associated with altered gene expression. Here we used TumorGraftTM models wherein part of a patient’s tumor is removed and grafted into immune-deficient mice and conducted global gene expression and DNA methylation analysis. We show that malignant non-central nervous system tumor growth causes profound molecular alterations in the brain. Mice harbouring triple negative or progesterone positive breast cancer TumorGrafts exhibited altered gene expression, decreased levels of DNA methylation, increased levels of DNA hydroxymethylation, and oxidative stress in the prefrontal cortex. Interestingly, chemotherapy did not have any additional synergistic effects on the analyzed processes. The molecular changes observed in this study are known signs of neurodegeneration and brain aging. This study provides an important roadmap for future large-scale analysis of the molecular and cellular mechanisms of tumor brain.