Basic Mechanisms Underlying Postchemotherapy Cognitive Impairment
Abstract
It is clear that chemotherapeutic drugs produce cognitive deficits in humans. As it is not possible to measure neurogenesis in living humans, data must be obtained from experimental animals. So far, our data show that methotrexate reduces hippocampal neurogenesis. Thus, our animal model might be useful to determine which chemotherapeutic drugs would be likely to produce cognitive deficits in humans. The chemotherapeutic drug, methotrexate, impairs spatial working memory in our animal model, as reflected by decreased performance in the spontaneous task. The finding that cyclophosphamide affected neither cognitive function nor neurogenesis suggests not all chemotherapeutic drugs necessarily produce adverse cognitive effects in humans. If we identify drugs that reduce methotrexate-induced impairments in cognition and methotrexate-induced decreases in neurogenesis, we will be able to provide strong support for our hypothesis that chemotherapeutic agents produce cognitive impairment by disrupting hippocampal neurogenesis. As such, our animal model might be of utility to discover therapeutic strategies to prevent and/or treat the development of neurocognitive deficits in individuals undergoing cancer chemotherapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2009
- Accession Number
- ADA520093
Entities
People
- Robert N. Pechnick
Organizations
- Cedars-Sinai Medical Center