Neuroendocrine Changes in the Aging Reproductive Axis of Female Rhesus Macaques (Macaca mulatta)1

Downs, Jodi L.; Urbanski, Henryk F.

doi:10.1095/biolreprod.106.051839

Cited by 81 publications

(103 citation statements)

References 40 publications

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“…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).…”

supporting

confidence: 73%

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.

150

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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supporting

confidence: 73%

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.

150

208

View full text Add to dashboard Cite

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“…First, the usage of pre-or perimenopausal females meant that the animals may have had sufficient circulating E 2 to maintain normal cognitive function, and so any potential benefits of DHEA-derived E 2 may have been overshadowed by the endogenous ovary-derived E 2 . Second, because rhesus macaques undergo menopause relatively later in life than women, 8 3BHSD2 expression and activity may already have been highly attenuated in these animals despite their premenopausal status. Consequently, cognition-associated brain areas of premenopausal macaques may have limited capacity to perform the first step of the conversion of DHEA to E 2 .…”

Section: Introductionmentioning

confidence: 99%

Hormone Supplementation During Aging: How Much and When?

Sorwell

Garten

Renner

et al. 2012

Rejuvenation Research

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Circulating levels of dehydroepiandrosterone, a major adrenal steroid, show a marked age-related decrease in both humans and nonhuman primates. Because this decrease has been implicated in age-related cognitive decline, we administered supplementary dehydroepiandrosterone to perimenopausal rhesus macaques (Macaca mulatta) to test for cognitive benefits. Although recognition memory improved, there was no benefit to spatial working memory. To address the limitations of this study we developed a hormone supplementation regimen in aged male macaques that more accurately replicates the 24-hr androgen profiles of young animals. We hypothesize that this more comprehensive physiological hormone replacement paradigm will enhance cognitive function in the elderly.

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“…Like women, adult female rhesus macaques menstruate and eventually undergo menopause, which is characterized by a similar marked decline in circulating levels of estradiol and progesterone (Downs and Urbanski 2006). To address this question, in the present study we used adult and aged female rhesus macaques to investigate the impact of ovariectomy on T-cell homeostasis and the immune response to vaccination.…”

Section: Introductionmentioning

confidence: 99%

Accelerated immune senescence and reduced response to vaccination in ovariectomized female rhesus macaques

Engelmann

Barron

Urbanski

et al. 2010

AGE

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Aging is associated with a general dysregulation in immune function, commonly referred to as "immune senescence". Several studies have shown that female sex steroids can modulate the immune response. However, the impact of menopauseassociated loss of estrogen and progestins on immune senescence remains poorly understood. To help answer this question, we examined the effect of ovariectomy on T-cell homeostasis and function in adult and aged female rhesus macaques. Our data show that in adult female rhesus macaques, ovariectomy increased the frequency of naïve CD4 T cells. In contrast, ovariectomized (ovx) aged female rhesus macaques had increased frequency of terminally differentiated CD4 effector memory T cells and inflammatory cytokine-secreting memory T cells. Moreover, ovariectomy reduced the immune response (T-cell cytokine and IgG production) following vaccination with modified vaccinia ankara in both adult and aged female rhesus macaques compared to ovary-intact age-matched controls. Interestingly, hormone therapy (estradiol alone or in conjunction with AGE (2011) 33:275-289

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Neuroendocrine Changes in the Aging Reproductive Axis of Female Rhesus Macaques (Macaca mulatta)1

Cited by 81 publications

References 40 publications

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

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

Hormone Supplementation During Aging: How Much and When?

Accelerated immune senescence and reduced response to vaccination in ovariectomized female rhesus macaques

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