ETI

Pilot Project

Dara L. Dickstein
Dara L. Dickstein, PhD
Assistant Professor Neuroscience
Mount Sinai School of Medicine

Assessing cognitive decline during breast cancer

There is recent evidence that many cancer survivors, in particular, women receiving chemotherapy to treat breast cancer, experience difficulties with memory, concentration and clear thinking. Whereas many of the side effects of chemotherapy are well described and understood, little is known about the effects on the brain. Studies investigating the shape and size of the brain support this notion and have reported structural and functional changes in brain regions associated with memory in patients receiving chemotherapy. Studies in rodent models have also found that exposure to chemotherapeutic drugs cause impairments in learning and memory behavior. Despite the obvious importance of the effect of cancer and chemotherapy on cognition, little research has been done to address this issue. The overall hypothesis to be tested in this proposal is whether cancer progression and chemotherapeutic agents affect the structural morphology and spine density of neurons and cause the cognitive decline that has been reported in human patients. To achieve this we have established the method of generating metastatic cancers in mice. In addition, we have created customized software that allows for the accurate quantification of spine number, type and volume from cells injected with fluorescent dyes. Thus, the specific aims of this application are 1) to determine the potential paraneoplastic effect of cancers with and without chemotherapeutic drug treatment on the neuronal morphology and spine density of pyramidal neurons of the CA1 region of the hippocampus and 2) to characterize the changes in synaptic plasticity that occur during cancer development and chemotherapy treatment using high resolution electron microscopy. We feel this research is unique and will provide a greater understanding of the morphological and synaptic changes that occur in the brain as a result of cancer and chemotherapy and may contribute to the development of new, less toxic therapies.