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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG016765-13
Application #
8433383
Study Section
Special Emphasis Panel (ZAG1-ZIJ-9)
Project Start
Project End
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
13
Fiscal Year
2013
Total Cost
$386,076
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Type
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Milham, Michael P; Ai, Lei; Koo, Bonhwang et al. (2018) An Open Resource for Non-human Primate Imaging. Neuron 100:61-74.e2
Motley, Sarah E; Grossman, Yael S; Janssen, William G M et al. (2018) Selective Loss of Thin Spines in Area 7a of the Primate Intraparietal Sulcus Predicts Age-Related Working Memory Impairment. J Neurosci 38:10467-10478
Bliss-Moreau, Eliza; Baxter, Mark G (2018) Estradiol treatment in a nonhuman primate model of menopause preserves affective reactivity. Behav Neurosci 132:224-229
Garcia, Alexandra N; Depena, Christina; Bezner, Kelsey et al. (2018) The timing and duration of estradiol treatment in a rat model of the perimenopause: Influences on social behavior and the neuromolecular phenotype. Horm Behav 97:75-84
Beckman, Danielle; Baxter, Mark G; Morrison, John H (2018) Future directions in animal models of Alzheimer's disease. J Neurosci Res 96:1829-1830
Baxter, Mark G; Santistevan, Anthony C; Bliss-Moreau, Eliza et al. (2018) Timing of cyclic estradiol treatment differentially affects cognition in aged female rhesus monkeys. Behav Neurosci 132:213-223
Crimins, Johanna L; Puri, Rishi; Calakos, Katina C et al. (2018) Synaptic distributions of pS214-tau in rhesus monkey prefrontal cortex are associated with spine density, but not with cognitive decline. J Comp Neurol :
McEwen, Bruce S; Milner, Teresa A (2017) Understanding the broad influence of sex hormones and sex differences in the brain. J Neurosci Res 95:24-39
Nutsch, Victoria L; Bell, Margaret R; Will, Ryan G et al. (2017) Aging and estradiol effects on gene expression in the medial preoptic area, bed nucleus of the stria terminalis, and posterodorsal medial amygdala of male rats. Mol Cell Endocrinol 442:153-164
Garcia, Alexandra N; Bezner, Kelsey; Depena, Christina et al. (2017) The effects of long-term estradiol treatment on social behavior and gene expression in adult female rats. Horm Behav 87:145-154

Showing the most recent 10 out of 132 publications