Basic Mechanisms Underlying Postchemotherapy Cognitive Impairment
Abstract
Post-chemotherapy cognitive impairment ("chemobrain") has been most often associated and studied in patients who have received adjuvant treatment for breast cancer. It is clear that chemotherapeutic drugs can produce cognitive deficits in humans; however, the mechanism is not known. Neurogenesis, the formation of new nerve cells, occurs throughout adulthood and is under the control of cell cycle regulators. Because some chemotherapeutic agents act by inhibiting cell cycle progression, we hypothesize that some of these agents produce cognitive impairment by disrupting neurogenesis in the hippocampus. The experiments in this Concept grant began to develop and utilize an animal model to study the effects of chemotherapeutic drugs, such as methotrexate, on cognitive function and neurogenesis. Mice were treated with saline or chemotherapeutic drugs. Behavioral testing was carried out and hippocampal neurogenesis was assessed. Our results show that methotrexate impairs cognitive function and reduces hippocampal neurogenesis in support of our hypothesis. Our results set the groundwork for future studies that use our animal model to test and develop therapeutic strategies to prevent and/or treat cognitive deficit in patients who undergo cancer chemotherapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2010
- Accession Number
- ADA542183
Entities
People
- Robert N. Pechnick
Organizations
- Cedars-Sinai Medical Center