Effects of Breast Cancer Chemotherapy Agents on Brain Activity in Rats: Functional Imaging Studies

摘要

There is an increasing awareness that adjuvant chemotherapy administration for breast cancer and other malignancies can cause cognitive impairment or 'chemobrain' in a significant proportion of patients . Little is known regarding its cause or even its duration and/or permanence. Rodent models are available for studying toxicity from doxorubicin and other chemotherapeutic agents and behavioral impairment has been demonstrated using them. The overall goal of this project is to investigate this impairment at a mechanistic level by determining the effects of doxorubicin, one of the agents commonly used for the adjuvant chemotherapy of breast cancer, on brain function using functional magnetic resonance imaging (fMRI) and behavioral techniques in a rat model. Female rats are treated with doxorubicin weekly, for six weeks. One week later, they are behaviorally tested and imaged using fMRI. Measures will also be made in rats, one and three months after doxorubicin treatment. To date, we have observed that treatment with doxorubicin alters brain activation in response to both visual and somatosensory stimulation with the effects greatest in the visual system. In addition, doxorubicin significantly decreases functional connectivity in the rat visual system. This supports our hypothesis that treatment with doxorubicin will cause changes in neuronal functional activity that can be detected and quantified using fMRI methods. Furthermore, it is consistent with impaired visual cognitive processing reported after chemotherapy.