The over-arching aim of Core B is to provide to each Project, access to tissue and results relevant to the functional status of ovariectomized rats maintained in two experiments conducted in a standardized setting. In phases I and 11, five treatment regimens [vehicle, estrogen, diarylpropionitrile (DPN), progesterone, or estrogen + progesterone], implemented after 3 different post-ovariectomy delays, will be evaluated for their ability to reverse the functional deficits associated with OVX in young adult (4-month old) and after one delay in reproductive senescent (10 month old) rats. In a subsequent experiment (phase 111), the neuroprotective efficacy of the same treatment regimens will be assessed in the transient middle cerebral artery occlusion (tMCAO) model of stroke. The assessment of functional outcomes at the different post-ovariectomy delays will provide the critical data that allows the individual projects to relate changes in the functions of estrogen receptors, progesterone receptors and intracellular calcium channels, to specific periods of sensitivity or refractoriness to hormone receptor-targeted interventions. Core B will provide standardized implementation of the experimental variables;outcome assessments, environment, and animal husbandry needed for the project experiments, and provide for highly efficient leveraging of resources used by all projects, including staff and animals. To this end. Core B will procure, identify and monitor rats used in the experiments, perform all surgical interventions (ovariectomy, implantation of Silastic pellets and tMCAO), and perform comprehensive analyses of the functional status of the rats in the context of the different treatment regimens. Core B will in addition provide non-behaviorally characterized rats that will have been ovariectomized and exposed to the 5 treatment to Project 2 for synaptoneurosomal fraction preparation, and will maintain availability of neonatal brain tissue for the generation of primary neuronal cultures.

Public Health Relevance

The ovariectomized rat is an experimental model that will allow the investigators to study how hormones support healthy brain function, ultimately leading to the design of effective hormone based therapy for treating brain dysfunction in humans. The transient middle cerebral artery occlusion (tMCAO) model simulates conditions of a stroke-related injury, and is also used to predict the efficacy of hormone therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG027956-06
Application #
8589550
Study Section
Special Emphasis Panel (ZAG1-ZIJ-9)
Project Start
Project End
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
6
Fiscal Year
2014
Total Cost
$224,720
Indirect Cost
$69,741
Name
University of North Texas
Department
Type
DUNS #
110091808
City
Fort Worth
State
TX
Country
United States
Zip Code
76107
Means, John C; Gerdes, Bryan C; Kaja, Simon et al. (2016) Caspase-3-Dependent Proteolytic Cleavage of Tau Causes Neurofibrillary Tangles and Results in Cognitive Impairment During Normal Aging. Neurochem Res 41:2278-88
Bukeirat, Mimi; Sarkar, Saumyendra N; Hu, Heng et al. (2016) MiR-34a regulates blood-brain barrier permeability and mitochondrial function by targeting cytochrome c. J Cereb Blood Flow Metab 36:387-92
Engler-Chiurazzi, E B; Singh, M; Simpkins, J W (2016) Reprint of: From the 90׳s to now: A brief historical perspective on more than two decades of estrogen neuroprotection. Brain Res 1645:79-82
Sun, Jiahong; Ren, Xuefang; Qi, Wen et al. (2016) Geissoschizine methyl ether protects oxidative stress-mediated cytotoxicity in neurons through the 'Neuronal Warburg Effect'. J Ethnopharmacol 187:249-58
Engler-Chiurazzi, E B; Singh, M; Simpkins, J W (2016) From the 90's to now: A brief historical perspective on more than two decades of estrogen neuroprotection. Brain Res 1633:96-100
Engler-Chiurazzi, E B; Brown, C M; Povroznik, J M et al. (2016) Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury. Prog Neurobiol :
Petrone, Ashley B; O'Connell, Grant C; Regier, Michael D et al. (2016) The Role of Arginase 1 in Post-Stroke Immunosuppression and Ischemic Stroke Severity. Transl Stroke Res 7:103-10
Sarkar, S; Jun, S; Rellick, S et al. (2016) Expression of microRNA-34a in Alzheimer's disease brain targets genes linked to synaptic plasticity, energy metabolism, and resting state network activity. Brain Res 1646:139-51
Hu, Heng; Doll, Danielle N; Sun, Jiahong et al. (2016) Mitochondrial Impairment in Cerebrovascular Endothelial Cells is Involved in the Correlation between Body Temperature and Stroke Severity. Aging Dis 7:14-27
Strong, Randy; Miller, Richard A; Antebi, Adam et al. (2016) Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer. Aging Cell 15:872-84

Showing the most recent 10 out of 111 publications