Mark Spritzer, Associate Professor, Chair of Department of Biology

Mark Spritzer

Topic: Testing the effects of testosterone replacement on spatial memory in a rat model of the aged male

Abstract:

Testosterone declines with age in men, and androgen deprivation therapy increases risk of dementia, implicating testosterone as a cause of age-related memory loss. We previously demonstrated that certain doses of testosterone improve spatial memory in castrated young adult male rats. To test the relationships between testosterone levels, age, and cognitive ability, we tested aged (20 months old) and young (2 months old) rats using the object-location memory task (OLMT) and a reference-working memory version of the radial-arm maze (RAM). Initial experiments involved comparisons between aged and young rats that were either castrated or sham-castrated. For the OLMT, neither of the aged groups were able to perform the task, whereas among the young rats, the sham group performed better than the castrated group. These results suggest that both increased age and lack of testosterone impair spatial memory. This conclusion was supported by the results of the RAM experiment, which showed that aged rats performed significantly more working memory errors than young rats and that castration further impaired spatial memory specifically among the aged rats. Subsequent experiments involved testing injections of a wide dose range of testosterone propionate (0.125, 0.250, 0.500, and 1.00 mg/rat) to determine if the effects of testosterone on memory were dose dependent. For the OLMT experiment, the 0.250 mg T group was the only group to successfully perform the task. For the RAM experiment, specific testosterone replacement doses (0.125, 0.500, 1.000 mg T) significantly reduced working memory errors compared to the other groups. In combination, these experiments indicated that testosterone replacement caused dose-dependent improvements in spatial memory, but the optimal dose varies with the specific type of memory. We have begun to explore the underlying mechanism by which testosterone improves memory, specifically assaying brain tissue (prefrontal cortex, hippocampus, and striatum) for levels of growth factors. Overall, the results indicate that testosterone replacement therapy may be a useful way to reduce the effects of age-related memory loss, but dose needs to be considered carefully.

 

Biography:

I am broadly interested in both how selective pressures have shaped behavioral traits and the underlying physiological mechanisms that lead to individual differences in behavior.

The focus of my research is the effects of hormones and social interactions on spatial cognition and adult neurogenesis (new nerve growth), using rats as a model system. We have shown that low testosterone levels impair adult neurogenesis and we have begun to test how other hormones (e.g., prolactin) and social interactions (e.g., sexual and agonistic) influence neurogenesis. The function of these new neurons remains controversial, and we have begun to examine the effects of testosterone on spatial learning and memory using a variety of maze tasks. We have shown that elevated testosterone can improve spatial memory, but the link to neurogenesis remains to be demonstrated. Finally, we are also examining levels of neurogenesis in wild populations of meadow voles. Research in my laboratory has implications for the treatment of a variety of neurodegenerative diseases, and students working with me gain practical experience conducting research projects involving a wide range of techniques: behavioral testing, surgical techniques, immunohistochemistry, hormone assays, and microscopy. The courses I teach involve hands-on laboratory exercise and a variety of discussion and lecture approaches to explore the biological complexity of animals: Animal Physiology, Comparative Vertebrate Biology, Sexual Selection, Endocrinology, and Animal Behavior.

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