Project activities include a recently published study in which we evaluated, in aged surgically menopausal rhesus monkeys, the cognitive effects of four hormone therapy (HT) regimens designed to mimic treatments used clinically in women (Baxter et al., 2013). Whereas our earlier work had demonstrated that monthly acute estrogen injection benefits working memory capacities mediated by the prefrontal cortex in aged ovariectormized monkeys, HT in women has often failed to improve cognitive function in clinical studies. The possibility that this discrepancy reflects differences in the formulation and timing of HT regimens, however, has not been tested systematically. Notably, none of the four hormone treatments examined in our experiments produced any beneficial effects on cognition, despite documented efficacy measured by serum hormone levels. Consistent with these findings, and in contrast to our previous results in brains from animals provided cyclic estrogen administration, none of the HT regimens tested had any detectable effect on dendritic spine density in the monkey prefrontal cortex (Ohm et al., 2013). Continuing work on this project is testing whether there is a window of opportunity for protecting cognitive function after ovarian hormone decline, together with a variety of related questions concerning the brain morphometric influence of surgical menopause and hormone therapy.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Investigator-Initiated Intramural Research Projects (ZIA)
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National Institute on Aging
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Hara, Yuko; Yuk, Frank; Puri, Rishi et al. (2016) Estrogen Restores Multisynaptic Boutons in the Dorsolateral Prefrontal Cortex while Promoting Working Memory in Aged Rhesus Monkeys. J Neurosci 36:901-10
Crimins, Johanna L; Wang, Athena Ching-Jung; Yuk, Frank et al. (2016) Diverse Synaptic Distributions of G Protein-coupled Estrogen Receptor 1 in Monkey Prefrontal Cortex with Aging and Menopause. Cereb Cortex :
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; Nguyen, Long T; Merceron, Tyler K et al. (2014) G-protein coupled estrogen receptor, estrogen receptor α, and progesterone receptor immunohistochemistry in the hypothalamus of aging female rhesus macaques given long-term estradiol treatment. J Exp Zool A Ecol Genet Physiol 321:399-414
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
Baxter, Mark G; Roberts, Mary T; Gee, Nancy A et al. (2013) Multiple clinically relevant hormone therapy regimens fail to improve cognitive function in aged ovariectomized rhesus monkeys. Neurobiol Aging 34:1882-90
Ohm, Daniel T; Bloss, Erik B; Janssen, William G et al. (2012) Clinically relevant hormone treatments fail to induce spinogenesis in prefrontal cortex of aged female rhesus monkeys. J Neurosci 32:11700-5
Hara, Yuko; Rapp, Peter R; Morrison, John H (2012) Neuronal and morphological bases of cognitive decline in aged rhesus monkeys. Age (Dordr) 34:1051-73
Dumitriu, Dani; Hao, Jiandong; Hara, Yuko et al. (2010) Selective changes in thin spine density and morphology in monkey prefrontal cortex correlate with aging-related cognitive impairment. J Neurosci 30:7507-15
Wang, Athena C J; Hara, Yuko; Janssen, William G M et al. (2010) Synaptic estrogen receptor-alpha levels in prefrontal cortex in female rhesus monkeys and their correlation with cognitive performance. J Neurosci 30:12770-6