Effects of ovarian hormones on cognitive function in nonhuman primates

Lacreuse, Agnès

doi:10.1016/j.neuroscience.2005.09.006

Cited by 80 publications

(56 citation statements)

References 91 publications

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“…Daniel and colleagues (Daniel et al 2006) showed that if E2 is administered to rats immediately following ovarectomy, improvements are seen in acquisition and delay trials of a working memory task, but not seen if E2 administration is delayed for up to five months. However some primate studies have shown that E2 benefits cognitive performance even when administration is delayed after ovarectomy or natural menopause even for several years (Lacreuse 2006;Lacreuse et al 2002;Rapp et al 2003). The reason for this discrepancy is not clear, but the length of the "window" or critical period may be quite different depending on the natural lifespan of the animal.…”

Section: Discussionmentioning

confidence: 99%

Estradiol interacts with the cholinergic system to affect verbal memory in postmenopausal women: Evidence for the critical period hypothesis

Dumas

Hancur-Bucci

Naylor

et al. 2008

Hormones and Behavior

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Estradiol has been shown to interact with the cholinergic system to affect cognition in postmenopausal women. This study further investigated the interaction of estradiol and cholinergic system functioning on verbal memory and attention in two groups of healthy younger (ages 50-62) and older (ages 70-80) postmenopausal women. Twenty-two postmenopausal women were randomly and blindly placed on 1 mg of 17-beta estradiol orally for one month then 2 mg for two months or matching placebo pills after which they participated in three anticholinergic challenge sessions when verbal memory performance was assessed. Subjects were administered either the antimuscarinic drug scopolamine (SCOP), the antinicotinic drug mecamylamine (MECA) or placebo. After the first challenge phase, they were crossed over to the other hormone treatment for another three months and repeated the challenges. Results showed that estradiol pretreatment significantly attenuated the anticholinergic drug-induced impairments on a test of episodic memory (the Buschke Selective Reminding test) for the younger group only, while estradiol treatment impaired performance of the older group. The results suggest that younger subjects may experience more cholinergic benefit from estradiol treatment than older subjects, supporting the concept of a critical period for postmenopausal estrogen use.

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Section: Discussionmentioning

confidence: 99%

Estradiol interacts with the cholinergic system to affect verbal memory in postmenopausal women: Evidence for the critical period hypothesis

Dumas

Hancur-Bucci

Naylor

et al. 2008

Hormones and Behavior

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“…2). Also, age appears to be an important contributor in that parallel research in young adult monkeys has reported more subtle, task-selective effects of estradiol (Voytko, 2002;Lacreuse, 2006), and our ongoing analyses of young animals with the same long-term-cyclic ET as these aged animals are not showing the same dramatic difference between treated and untreated groups in prefrontal tasks (Hao et al, this meeting).…”

Section: Long-term Cyclical Et Enhances Cognitive Performance and Spimentioning

confidence: 95%

“…), as well as its capacity to be neuroprotective (Bryant et al, 2006). In addition, animal studies have demonstrated positive effects of ET on cognitive behavior, particularly in nonhuman primates (NHPs), although the extent and nature of cognitive enhancement varies with age (Lacreuse, 2006).…”

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confidence: 99%

“…Thus, we are in the midst of an intense reevaluation of both the clinical studies and the preclinical studies, with an emerging consensus that each must inform the other in a more directed manner than in the past. From this perspective, the animal models of ET and/or HT have never been more important (Adams et al, 2001b;Gore, 2001;Bellino and Wise, 2003;Gibbs and Gabor, 2003;Turgeon et al, 2004;Brinton, 2005;Lacreuse, 2006). In the 36th Annual Meeting of the Society for Neuroscience presentations and the four sections below (designated by presenter/author initials), we have attempted to provide insight into the current clinical issues surrounding menopause and HT/ET with respect to the brain, as well as a preclinical perspective on hypothalamic control of reproductive aging, synaptic effects of estradiol related to cognitive performance, and analyses of the cellular mechanisms of ovarian hormones.…”

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confidence: 99%

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Estrogen, Menopause, and the Aging Brain: How Basic Neuroscience Can Inform Hormone Therapy in Women

Morrison¹,

Brinton²,

Schmidt³

et al. 2006

J. Neurosci.

312

242

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IntroductionAs neuroscientists, we can be so taken by the complexity and unique capabilities of the brain that we occasionally forget that it is part of a larger integrated biological system reliant on signaling and communication throughout the organism. The interactions between key organs that release hormones (e.g., gonads) and the nervous system are an excellent reflection of this "whole-brain, whole-body" level of integration. For example, effects of estrogens such as 17-␤-estradiol (the major estrogen in most mammals, including women, referred to henceforward as estradiol) on a broad array of brain regions and the widespread distribution of estrogen receptors throughout the entire brain highlight the extraordinary integrative power of this hormone. An important concept in this interaction is that the brain both controls estrogen release through the hypothalamus-pituitary-gonadal (HPG) axis and responds to estrogen. Neuroendocrine function initiates in the hypothalamus (see below, section by A.C.G.) (Fig. 1), but the circuits that respond to estrogens go well beyond the hypothalamus to include neocortex, hippocampus, and brainstem. In addition, estradiol plays a key role in the neurobiology of aging, because endocrine and neural senescence overlap in time and are mechanistically intertwined in complex feedback loops. This aspect of aging is fundamental for humans, because all women will experience a dramatic drop in circulating estrogens if they live long enough to reach the menopause transition. Interestingly, at the turn of the past century, both life expectancy and the average age of onset of menopause for women in America was slightly over 50 years, whereas currently women can expect to live until 80 years of age, although the average age of menopause remains in

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“…However, the emerging story in aged nonhuman primates differs in important ways from the rodent findings (20). First, the available evidence suggests that the cognitive benefit of E in aged OVX monkeys is substantially greater than in young adults, particularly on tests emphasizing dlPFC integrity (21). A previous study, for example, reported that performance on the dlPFC-dependent delayed response (DR) is not enhanced by continuous E treatment in OVX young monkeys (22).…”

mentioning

confidence: 99%

Interactive effects of age and estrogen on cognition and pyramidal neurons in monkey prefrontal cortex

Hao

Rapp

Janssen

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

153

208

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We previously reported that long-term cyclic estrogen (E) treatment reverses age-related impairment of cognitive function mediated by the dorsolateral prefrontal cortex (dlPFC) in ovariectomized (OVX) female rhesus monkeys, and that E induces a corresponding increase in spine density in layer III dlPFC pyramidal neurons. We have now investigated the effects of the same E treatment in young adult females. In contrast to the results for aged monkeys, E treatment failed to enhance dlPFC-dependent task performance relative to vehicle control values (group young OVX؉Veh) but nonetheless led to a robust increase in spine density. This response was accompanied by a decline in dendritic length, however, such that the total number of spines per neuron was equivalent in young OVX؉Veh and OVX؉E groups. Robust effects of chronological age, independent of ovarian hormone status, were also observed, comprising significant age-related declines in dendritic length and spine density, with a preferential decrease in small spines in the aged groups. Notably, the spine effects were partially reversed by cyclic E administration, although young OVX؉Veh monkeys still had a higher complement of small spines than did aged E treated monkeys. In summary, layer III pyramidal neurons in the dlPFC are sensitive to ovarian hormone status in both young and aged monkeys, but these effects are not entirely equivalent across age groups. The results also suggest that the cognitive benefit of E treatment in aged monkeys is mediated by enabling synaptic plasticity through a cyclical increase in small, highly plastic dendritic spines in the primate dlPFC.aging ͉ estradiol ͉ hormone ͉ neocortex ͉ plasticity N umerous studies have demonstrated that E affects synaptic structure and function in multiple brain regions important for memory and cognition (1). In the hippocampus of young female rats, 17␤-estradiol [the dominant estrogen (E) in rats, monkeys, and humans] increases the density of dendritic spines and axospinous synapses on CA1 pyramidal cells (2, 3). These effects are N-methyl-D-aspartate (NMDA) receptor-dependent (4), and E both directly increases NMDA receptor levels and facilitates NMDA receptor-mediated responses in CA1 pyramidal neurons (5, 6). E also affects GABAergic (7) and cholinergic (8) systems in the CA1 field of the young female rat hippocampus. The data from young adult monkeys are generally consistent with these observations, which is particularly relevant to humans given the reported similarities in cyclicity and menopause between women and female rhesus monkeys (9, 10). Of particular note, E increases CA1 spine number in ovariectomized (OVX) young African green (11) and rhesus monkeys (12). Estrogen administration also increases spine number in layer I of dorsolateral prefrontal cortex (dlPFC) of young rhesus monkeys (13) and enhances cholinergic and monoaminergic inputs to this region (14, 15), demonstrating that potential targets for ovarian hormone influences on cognitive function extend beyond the hippocampus in primates.G...

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Effects of ovarian hormones on cognitive function in nonhuman primates

Cited by 80 publications

References 91 publications

Estradiol interacts with the cholinergic system to affect verbal memory in postmenopausal women: Evidence for the critical period hypothesis

Estradiol interacts with the cholinergic system to affect verbal memory in postmenopausal women: Evidence for the critical period hypothesis

Estrogen, Menopause, and the Aging Brain: How Basic Neuroscience Can Inform Hormone Therapy in Women

Interactive effects of age and estrogen on cognition and pyramidal neurons in monkey prefrontal cortex

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