Androgen Deprivation Therapy and Cognitive Impairment
Abstract
Androgen deprivation therapy is a well-established treatment for prostate cancer, but an important side effect of androgen deprivation therapy is impairment of memory and learning. The goal of this project was to use an animal model to test the hypothesis that impaired adult hippocampal neurogenesis underlies the androgen deprivation therapy-induced impairment of cognitive function. We found that three approaches used to reduce androgenic activity in patients suffering from prostate cancer (i.e., castration, leuprolide and flutamide) all decrease neuronal proliferation and neuronal survival in the dentate gyrus of the hippocampus in mice. Although adult hippocampal neurogenesis is thought to underlie various forms of memory and learning, especially spatial memory, the results of the experiments provided no evidence that androgen deprivation produces deficits in cognitive function. Both the serotonin-selective reuptake inhibitor antidepressant fluoxetine and the uncompetitive N-methyl-D-aspartate receptor antagonist memantine stimulate hippocampal neurogenesis. The results of the experiments show that fluoxetine can reverse castration-induced deficits in neuronal proliferation, but had no effect on neuronal survival. Therefore, the utility of these drugs in preventing or treating cognitive deficits in prostate cancer patients is questionable.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2020
- Accession Number
- AD1137208
Entities
People
- Robert N. Pechnick
Organizations
- Western University of Health Sciences