67 - Hormone Regulation of Adult Hippocampal Neurogenesis in the Mammalian Brain

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Steroid and peptide hormones modulate neurogenesis in the dentate gyrus differentially in male and female adult rodents. Neurogenesis is comprised of at least two components: cell proliferation (the production of new cells) and cell survival (which ultimately results in changes to the number of new neurons that survive to maturity). This chapter focuses on the effects of estrogens, androgens, adrenal steroids, and peptide hormones on hippocampal neurogenesis in the adult male and female rodent. Evidence is reviewed for the co-localization of hormone receptors with markers for neurogenesis to indicate possible mechanisms by which hormones exert their effects to modulate neurogenesis. Estradiol modulates hippocampal neurogenesis and cell death in adult female, but not male, rodents, while testosterone upregulates hippocampal neurogenesis in adult male rodents. Few studies have compared males and females, but existing research suggests a sex difference in the response to stress-regulated hippocampal neurogenesis in the adult. More work is needed to elucidate the effects of hormones on neurogenesis in the dentate gyrus of both male and female rodents across the life span. This is crucial if we are to use our knowledge of how adult neurogenesis is regulated to develop strategies to replace neuron loss in neurodegenerative diseases, which often exhibit sex differences in disease incidence, symptomology, and/or progression.

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Cindy Barha is a first year PhD student in Dr. Liisa Galea's laboratory at the University of British Columbia in Vancouver, Canada. Her research interests focus on the effects of different forms of estrogen on hippocampal plasticity and cognition across the life span. She received a BSc honors with distinction in 2006 at the University of Victoria and a MA at the University of British Columbia in 2007 under the supervision of Liisa Galea. Her thesis looked at the effect of naturally occurring variation in maternal care on learning and memory and stress reactivity in adult male and female offspring. Cindy holds a NSERC Postgraduate Scholarship and is a Pacific Century Scholar.

Jennifer Barker is a PhD candidate in Dr. Liisa Galea's laboratory at the University of British Columbia in Vancouver, Canada. She obtained her BSc honors with high distinction in 2001 at the University of Toronto, and her MSc at the University of Toronto at Scarborough in 2004 under the supervision of Dr. Rudy Boonstra. Her MSc thesis work compared adult neurogenesis in wild squirrels and chipmunks, and her current research work is focused on the effects of repeated estradiol exposure on adult neurogenesis and hippocampus-dependent learning, in both males and females. Jennifer's PhD work has been funded by an NSERC Canada Graduate Scholarship, and she currently holds a research trainee grant from the Alzheimer's Society of Canada.

Dr. Susanne Brummelte is a postdoctoral fellow in Dr. Liisa Galea's lab at the University of British Columbia in Vancouver, Canada. She received her doctoral degree in neurobiology with distinction in February 2007 from the University of Bielefeld in Germany under the supervision of Prof. Dr. Gertraud Teuchert-Noodt. Her dissertation thesis was focused on the effect of early acute or chronic stressors on different neurotransmitter systems in the gerbil brain.

Dr. Brummelte's research focuses on how stress and early life experience affect the development and plasticity of the nervous system. As a postdoctoral fellow, Susanne extended her work on an animal model of postpartum stress/depression (PPD), which she developed as a visiting researcher in 2004 in Dr. Galea's lab. This model provides the means to investigate the effects of high levels of stress hormones on the dams and on the outcome of the offspring, including changes in hippocampal neurogenesis. Susanne holds a postdoctoral research fellowship from the Canadian Government and is a former German National Academic Foundation scholar.

Jonathan Epp is a third-year PhD candidate in Dr. Liisa Galea's lab. His research focuses on the functional consequences of adult neurogenesis in the hippocampus. Specifically, the importance of adult-generated neurons to hippocampus-dependent learning and memory. He received his MSc in neuroscience from the University of Lethbridge under the supervision of Robert Sutherland. His thesis examined the factors that cause some types of memory to be vulnerable to retrograde and anterograde amnesia following hippocampus damage. Jonathan is a Michael Smith Foundation for Health Research Senior Graduate Trainee.

Dr. Galea has been studying hormonal control and function of adult neurogenesis in the hippocampus since 1994. She completed her PhD at the University of Western Ontario under the supervision of Drs. Martin Kavaliers and Peter Ossenkopp and then a postdoctoral fellowship at the Rockefeller University with Dr. Bruce McEwen. Dr. Galea is professor in the Department of Psychology at the University of British Columbia in Vancouver, Canada. She currently has funding from a variety of provincial and federal sources and holds a Michael Smith Senior Scholar award and a Discovery Accelerator Supplement from Natural Sciences and Engineering Research Council of Canada. She is the co-author of over 60 publications and several book chapters. Dr. Galea's research program investigates how steroid hormones influence hippocampal neurogenesis, learning and memory, emotional behavior, and synaptic plasticity. The overall objectives of her research are to clearly delineate the effects of ovarian and stress hormones on adult neurogenesis and cognition and to determine whether these hormones enhance cognition through its effects on hippocampal neurogenesis or synaptic alterations. In the long term, her work may provide the necessary clues to aid in the development of therapeutic measures for enhancing cognition, alleviating depression, and in promoting and enticing new neurons into brain areas that have suffered neuronal loss.

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