Androgen Deprivation Therapy and Cognitive Impairment
[Technical Report, Annual Report]
Western University of Health Sciences
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Androgen deprivation therapy is used in the treatment of prostate cancer, but an important side effect is impairment of memory and learning. In the hippocampus, a brain region involved in memory and learning, new nerve cells i.e., neurons continue to develop throughout adulthood, a process is called adult neurogenesis. The goal of this project is to test the hypothesis that impaired hippocampal neurogenesis underlies the androgen deprivation therapy-induced impairment of cognitive function. We carried out castration surgeries or implanted pellets containing leuprolide a gonadotropin-releasing hormone analog that reduces plasma testosterone levels and flutamide an androgen receptor antagonist. We found that these three approaches, that are used in prostate cancer patients, significantly reduced both the proliferation and survival of new neurons in the hippocampus. These results suggest that androgen-deprivation might cause similar deficits in hippocampal neurogenesis in prostate cancer patients We also found that androgen deprivation does not affect neurogenesis in the subventricular zone, demonstrating that the effects are limited to the hippocampus. Experiments have been completed testing whether the effects can be reversed by drug treatment and the results currently are being analyzed.
- Anatomy and Physiology