During the current funding period, we examined in detail the effects of ERT on a variety of markers of the cholinergic basal forebrain system as well as dopaminergic mesocortical and nigrostriatal circuits. Effects were few. The effects that were limited to modest alterations in the vertical limb of the diagonal band (VLDB) and cholinergic innervation of cortex. Many of the discrepancies with respect to these systems could be due to the specific parameters employed such as the dose and schedule of estrogen replacement therapy (ERT). The failure to replicate findings in monkeys previously seen in rodents could also be due to species differences in response to ERT and highlights the need to study estrogen-related processes in a species close to humans. However, in the present proposal, we chose to change directions rather than pursue effects of ERT in primate systems for which robust findings cannot be demonstrated in our model. Instead this new direction focuses on ERT's effects of neurogenesis in monkeys, an exciting finding seen in lower species. We know that ERT influences neurogenesis in rats and we know that neurogenesis occurs in monkeys throughout their lifetime, however, there are no data available on the effect of ERT on neurogenesis in nonhuman primates. Thus it is logical to test the potency of ERT in altering neurogenesis in nonhuman primates, in addition, we will have the opportunity to pursue these studies in a parallel group of monkeys that have ERT+progesterone (P), and thus will be able to determine if P counters any positive effects of ERT on neurogenesis. We will also determine whether the pattern of hormone delivery, that being cyclic or chronic E and P delivery influences neurogenesis in nonhuman primates. Finally, multiple markers for neuroanatomic analyses and single cell gene arrays will be used to characterize the newly differentiated neurons in great detail to reveal their functional and circuitry properties. Given this total change of direction, we feel it is appropriate to request only 3 years of support at this time. Should the experiments in this funding period bear fruit, we will ask for an additional 2 years of funding in a supplement.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG016765-08
Application #
7409670
Study Section
Special Emphasis Panel (ZAG1)
Project Start
Project End
Budget Start
2007-03-01
Budget End
2008-02-29
Support Year
8
Fiscal Year
2007
Total Cost
$326,921
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Type
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
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; Will, Ryan G; Tobiansky, Daniel J et al. (2017) Age-related changes in sexual function and steroid-hormone receptors in the medial preoptic area of male rats. Horm Behav 96:4-12
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
Marques-Lopes, Jose; Tesfaye, Ephrath; Israilov, Sigal et al. (2017) Redistribution of NMDA Receptors in Estrogen-Receptor-?-Containing Paraventricular Hypothalamic Neurons following Slow-Pressor Angiotensin II Hypertension in Female Mice with Accelerated Ovarian Failure. Neuroendocrinology 104:239-256
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
Almey, Anne; Milner, Teresa A; Brake, Wayne G (2016) Estrogen receptor ? and G-protein coupled estrogen receptor 1 are localized to GABAergic neurons in the dorsal striatum. Neurosci Lett 622:118-23
Mazid, Sanoara; Hall, Baila S; Odell, Shannon C et al. (2016) Sex differences in subcellular distribution of delta opioid receptors in the rat hippocampus in response to acute and chronic stress. Neurobiol Stress 5:37-53
Naugle, Michelle M; Lozano, Sateria A; Guarraci, Fay A et al. (2016) Age and Long-Term Hormone Treatment Effects on the Ultrastructural Morphology of the Median Eminence of Female Rhesus Macaques. Neuroendocrinology 103:650-64
Garcia, Alexandra N; Depena, Christina K; Yin, Weiling et al. (2016) Testing the critical window of estradiol replacement on gene expression of vasopressin, oxytocin, and their receptors, in the hypothalamus of aging female rats. Mol Cell Endocrinol 419:102-12
Marques-Lopes, Jose; Lynch, Mary-Katherine; Van Kempen, Tracey A et al. (2015) Female protection from slow-pressor effects of angiotensin II involves prevention of ROS production independent of NMDA receptor trafficking in hypothalamic neurons expressing angiotensin 1A receptors. Synapse 69:148-65

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