Investigating the Mechanism of Methotrexate-induced Neurotoxicity

Background

It has been previously established that intrathecal methotrexate administration in patients with acute lymphoblastic leukemia or non-Hodgkin lymphoma is associated with neurotoxic side effects concerning cognitive function. The drug memantine, which is currently used to treat dementia related to Alzheimer’s disease, was tested on rats treated with intrathecal methotrexate. The study showed that it protected them from developing spatial memory deficits. However, it is unknown the exact mechanism through which the memantine prevents cognitive dysfunctions.

Project Goal

Alexander will be working to further investigate the mechanism in which memantine protects cognitive function. He will do this by measuring markers of oxidative stress in rats in different intervention groups, as previous studies have shown that methotrexate-induces neurotoxicity may be associated with oxidative stress. It is hypothesized that if memantine protected cognitive function through an oxidative stress pathway, there will be fewer markers of oxidative stress in the group receiving memantine and methotrexate. If this is not the case, then their evidence will further support the previous hypothesis that memantine is preserving cognitive function solely by antagonizing NMDA receptors.