Cognitive aging in women is closely related to age-related changes in neuroendocrine systems, particulariy the loss of circulating ovarian steroid hormones that occurs in menopause. Surprising findings from the Women's Health Initiative Memory Study showed that hormone treatment (HT) begun long after the onset of menopause failed to improve cognition and may have been harmful. This contrasts with other studies indicating beneficial cognitive effects of HT begun soon after the onset of menopause. To reconcile these findings a 'window of opportunity'hypothesis has been proposed, such that there is a limited period of fime after menopause during which HT may improve cognifion. Because of other health risks associated with long-term HT including cardiovascular disease and cancer, current advice is for women to take a short course of HT at the onset of menopause and then disconfinue it. We will test, in a well-characterized animal model, whether beneficial cognitive effects of HT (on spatiotemporal working memory, visual recognition memory, and vulnerability to distraction) persist after discontinuation of HT, and whether they are sfill observed when HT is begun after a long delay post-menopause. In vivo neuroimaging analyses conducted concurrently with behavioral tesfing will measure neurobiological changes in parallel with cognitive ability. This study will test the 'window of opportunity'hypothesis explicitly, as well as whether cognitiye benefits can be maintained after withdrawal of HT. These studies will provide critical translational insights into how HT can improve cognitive outcomes of aging.

Public Health Relevance

Hormone replacement therapy in women after menopause can improve brain funcfion, including memory. We will test, in an animal model, how the fiming of hormone therapy after menopause affects its ability to improve brain function, both in terms of whether therapy must begin soon after menopause to be effective, and whether its beneficial effects persist after therapy is discontinued. These studies will help us maintain best brain and memory function in women as they age.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG016765-13
Application #
8433388
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
$532,440
Indirect Cost
$66,464
Name
Icahn School of Medicine at Mount Sinai
Department
Type
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
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

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