The middle-aged ovariectomized marmoset (Callithrix jacchus) as a model of menopausal symptoms: Preliminary evidence

Gervais, Nicole; Viechweg, Shaun S.; Mong, Jessica A.; Lacreuse, Agnès

doi:10.1016/j.neuroscience.2016.08.056

Cited by 11 publications

(7 citation statements)

References 47 publications

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“…Menopause in humans is marked by HFs. As previously mentioned, E2 has been associated with lower nighttime core body temperature and more restorative sleep in middle/older-aged OVX marmosets ( 88 ). Since both body temperature and sleep are sensitive to circadian timing, these results suggest that ovarian hormones may play a crucial role in modulating circadian rhythmicity.…”

Section: Role Of E2 In Circadian Regulation Of the Sleep–wake Cyclementioning

confidence: 89%

“…Further, middle-aged OVX marmosets given E2 replacement demonstrate lower nighttime core body temperature, fewer nighttime arousals, and higher SWA ( Fig. 1 ), signifying more intense and restorative sleep ( 88 ). At first glance, these findings seem contradictory to studies in women, which show that menopause (and therefore ovarian hormone deprivation) is associated with increased SWS.…”

Section: Contributions Of Menopause-associated Hormone Changes To Slementioning

confidence: 98%

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Role of Ovarian Hormones in the Modulation of Sleep in Females Across the Adult Lifespan

Brown

Gervais

2020

Endocrinology

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Ovarian hormones, including 17β-estradiol, are implicated in numerous physiological processes, including sleep. Beginning at puberty, girls report more sleep complaints than boys, which is maintained throughout the reproductive life stage. Sleep problems are exacerbated during the menopausal transition, evidenced by greater risk for sleep disorders. There is emerging evidence that menopause-associated hormone loss contributes to this elevated risk, but age is also an important factor. The extent to which menopause-associated sleep disturbance persists into postmenopause above and beyond the effects of age remains unknown. Untreated sleep disturbances have important implications for cognitive health, as they are emerging as risk factors for dementia. Given that sleep loss impairs memory, an important knowledge gap concerns the role played by menopause-associated hormone loss in exacerbating sleep disturbance and ultimately, cognitive function in aging women. In this review, we take a translational approach to illustrate the contribution of ovarian hormones in maintaining the sleep-wake cycle in younger and middle-aged females, with evidence implicating 17β-estradiol in supporting the memory-promoting effects of sleep. Sleep physiology is briefly reviewed before turning to behavioural and neural evidence from young females linking 17β-estradiol to sleep-wake cycle maintenance. Implications of menopause-associated 17β-estradiol loss is also reviewed before discussing how ovarian hormones may support the memory-promoting effects of sleep, and why menopause may exacerbate pathological aging via effects on sleep. While still in its infancy, this research area offers a new sex-based perspective on aging research, with a focus on a modifiable risk factor for pathological aging.

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Section: Role Of E2 In Circadian Regulation Of the Sleep–wake Cyclementioning

confidence: 89%

Section: Contributions Of Menopause-associated Hormone Changes To Slementioning

confidence: 98%

Role of Ovarian Hormones in the Modulation of Sleep in Females Across the Adult Lifespan

Brown

Gervais

2020

Endocrinology

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“…To prevent this conversion, women with estrogen receptor (ER)-dependent breast cancers are often given aromatase inhibitors (AIs) as an adjuvant therapy for many years (Burstein et al, 2014;Chumsri et al, 2016). AIs are associated with side effects that impair quality of life, including insomnia (Desai et al, 2013), hot flashes (Rand et al, 2011), depression (Chumsri et al, 2016, and memory deficits (Bender et al, 2007;Blaustein, 2017; but see Ganz et al, 2016). For example, reduced hippocampal (HPC) activity and increased PFC activity, along with slightly diminished memory, were reported in women taking letrozole (Bayer et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Adverse Effects of Aromatase Inhibition on the Brain and Behavior in a Nonhuman Primate

et al. 2018

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Breast cancer patients using aromatase inhibitors (AIs) as an adjuvant therapy often report side effects, including hot flashes, mood changes, and cognitive impairment. Despite long-term use in humans, little is known about the effects of continuous AI administration on the brain and cognition. We used a primate model of human cognitive aging, the common marmoset, to examine the effects of a 4-week daily administration of the AI letrozole (20 g, p.o.) on cognition, anxiety, thermoregulation, brain estrogen content, and hippocampal pyramidal cell physiology. Letrozole treatment was administered to both male and female marmosets and reduced peripheral levels of estradiol (E2), but unexpectedly increased E2 levels in the hippocampus. Spatial working memory and intrinsic excitability of hippocampal neurons were negatively affected by the treatment possibly due to increased hippocampal E2. While no changes in hypothalamic E2 were observed, thermoregulation was disrupted by letrozole in females only, indicating some impact on hypothalamic activity. These findings suggest adverse effects of AIs on the primate brain and call for new therapies that effectively prevent breast cancer recurrence while minimizing side effects that further compromise quality of life.

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“…Undoubtedly, bone of marmoset monkeys shows close similarities to human bone (Bagi et al, 2007;Grohmann et al, 2012), responds to standard therapeutics (Bagi et al, 2007), and is a valuable addition for preclinical research. Moreover, other menopausal symptoms such as hot flashes and sleep disturbances could also show to be inducible by estrogen withdrawal in the marmoset monkey (Gervais et al, 2016). These findings open an additional window for holistic approaches in preclinical drug testing which in the best case can answer more than one question about the efficacy of new therapies.…”

Section: Discussionmentioning

confidence: 93%

Effect of ovariectomy on proximal tibia metaphysis and lumbar vertebral body in common marmoset monkeys

2019

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Abstract. This study aimed to investigate the effect of estrogen withdrawal on bone tissue in adult female marmoset monkeys. In a 1-year follow-up study we used quantitative computer tomography to measure total bone mineral density (BMD) of the proximal tibia and the second-last lumbar vertebral body (L5/L6) before and 1, 3, 6, and 12 months after ovariectomy. Body mass did not significantly change during the 1-year observation period. However, a significant decline of total BMD after ovariectomy was observed in the proximal tibia but not in L5/L6. In addition, regression analysis showed a significant positive relationship between BMD and body mass in both tibia and L5/L6. The results of our study support the idea that ovariectomized marmoset monkeys may serve as a model to investigate bone loss related to decline of estrogen production.

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The middle-aged ovariectomized marmoset (Callithrix jacchus) as a model of menopausal symptoms: Preliminary evidence

Cited by 11 publications

References 47 publications

Role of Ovarian Hormones in the Modulation of Sleep in Females Across the Adult Lifespan

Role of Ovarian Hormones in the Modulation of Sleep in Females Across the Adult Lifespan

Adverse Effects of Aromatase Inhibition on the Brain and Behavior in a Nonhuman Primate

Effect of ovariectomy on proximal tibia metaphysis and lumbar vertebral body in common marmoset monkeys

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