The Animal Core is essential for the extension of the concepts that have been developed during the previous funding periods. In this application the Animal Core continues to provide the unique nonhuman primate (NHP) animal model, a trained staff in NHP research as well as specific methodologies and services that are required to make appropriate and efficient use of this limited resource. Studies involving monkeys currently in protocol will be completed in early 2011 and additional aged female rhesus monkeys will enter protocols and be studied over the five-year funding period. Our current data demonstrate the importance of estrogen treatment (ET) for the maintenance of higher brain function and structure in the absence of normal ovarian function in aged female primates. However, these previous studies have not conclusively identified which modality of ET or combined hormone treatment (HT) regimens are most effective and specifically which effective modalities would be best for clinical applications. The monkeys currently in protocol are committed to these studies. The monkeys that will enter protocols over this funding period will be used to investigate the structural and functional repercussions of altering the time of onset and duration of treatment following ovariectomy (OVX). These studies will investigate two critically important clinical issues;1) Is there a "window of opportunity" following cessation of ovarian function after which the brain is less responsive to ET/HT, and 2) Do the cognitive benefits of ET/HT started soon after the loss of circulating sex steroids persist after treatment is halted? Resources provided by the Animal Core include clinical care, trained animal care staff, therapeutic support, surgery/necropsy services and endocrine services. In addition, the California National Primate Center (CNPRC) behavior and endocrine staff scientists have participated in the design of the experiments and will be involved in the execution of the total research plan. Appropriately, the current application addresses specific questions that cannot be ethically approached in clinical studies but are effectively addressed in a NHP model. These studies will provide new and important information and insights for designing critical studies in the future. In addition, the results from all of the experiments will have direct and important implications for improved therapies to insure healthy aging in women. Both the use of the NHP model and a Primate Center setting and staff are required in order to effectively conduct such experiments and guarantee the delivery of interpretable data.
The use of the nonhuman primate animal model is considered essential for investigations relating to the role of ovarian hormones in human aging and only a primate center facility and staff can provide the necessary resources and skills to conduct such studies. One of the most pressing issues in women's health is the efficacy and safety of estrogen replacement therapy for menopausal symptoms and cognitive health. This proposal provides the plan, resources and the expertise to conduct studies that address this issue.
|Marques-Lopes, Jose; Van Kempen, Tracey; Waters, Elizabeth M et al. (2014) Slow-pressor angiotensin II hypertension and concomitant dendritic NMDA receptor trafficking in estrogen receptor ?-containing neurons of the mouse hypothalamic paraventricular nucleus are sex and age dependent. J Comp Neurol 522:3075-90|
|McEwen, B S (2014) Sex, stress and the brain: interactive actions of hormones on the developing and adult brain. Climacteric 17 Suppl 2:18-25|
|Almey, Anne; Cannell, Elizabeth; Bertram, Kyla et al. (2014) Medial prefrontal cortical estradiol rapidly alters memory system bias in female rats: ultrastructural analysis reveals membrane-associated estrogen receptors as potential mediators. Endocrinology 155:4422-32|
|Picard, Martin; McEwen, Bruce S (2014) Mitochondria impact brain function and cognition. Proc Natl Acad Sci U S A 111:7-8|
|Morrison, John H; Baxter, Mark G (2014) Synaptic health. JAMA Psychiatry 71:835-7|
|Wu, Melody V; Shamy, Jul Lea; Bedi, Gillinder et al. (2014) Impact of social status and antidepressant treatment on neurogenesis in the baboon hippocampus. Neuropsychopharmacology 39:1861-71|
|Kermath, Bailey A; Riha, Penny D; Woller, Michael J et al. (2014) Hypothalamic molecular changes underlying natural reproductive senescence in the female rat. Endocrinology 155:3597-609|
|Hara, Yuko; Yuk, Frank; Puri, Rishi et al. (2014) Presynaptic mitochondrial morphology in monkey prefrontal cortex correlates with working memory and is improved with estrogen treatment. Proc Natl Acad Sci U S A 111:486-91|
|Young, M E; Ohm, D T; Dumitriu, D et al. (2014) Differential effects of aging on dendritic spines in visual cortex and prefrontal cortex of the rhesus monkey. Neuroscience 274:33-43|
|Naugle, Michelle M; Gore, Andrea C (2014) GnRH neurons of young and aged female rhesus monkeys co-express GPER but are unaffected by long-term hormone replacement. Neuroendocrinology 100:334-46|
Showing the most recent 10 out of 102 publications