Agnès Lacreuse - Academia.edu (original) (raw)

Papers by Agnès Lacreuse

Research paper thumbnail of Effect of menstrual cycle on resting brain metabolism in female rhesus monkeys

NeuroReport, 2008

Little is known about the effects of the menstrual cycle on brain activity in primates. Here, we ... more Little is known about the effects of the menstrual cycle on brain activity in primates. Here, we use 18F-fluorodeoxyglucose positron emission tomography to monitor changes in resting brain glucose metabolism across the menstrual cycle in female rhesus monkeys. Results showed greater activity in right lateral orbitofrontal cortex, a region involved in processing negatively valenced emotional stimuli, in the follicular compared with luteal phase. Estradiol levels were negatively correlated with activity in cortical and brainstem regions involved in emotional processing, and positively correlated with activity in areas involved in cognitive control and emotion regulation. In summary, the data suggest that in primates, fluctuations of ovarian hormones across the menstrual cycle influence activity in brain areas involved in emotion and its regulation.

Research paper thumbnail of The marmoset as an important primate model for longitudinal studies of neurocognitive aging

American Journal of Primatology

Age-related cognitive decline has been extensively studied in humans, but the majority of researc... more Age-related cognitive decline has been extensively studied in humans, but the majority of research designs are cross-sectional and compare across younger and older adults. Longitudinal studies are necessary to capture variability in cognitive aging trajectories but are difficult to carry out in humans and long-lived nonhuman primates. Marmosets are an ideal primate model for neurocognitive aging as their naturally short lifespan facilitates longitudinal designs. In a longitudinal study of marmosets tested on reversal learning starting in middle-age, we found that, on average, the group of marmosets declined in cognitive performance around 8 years of age. However, we found highly variable patterns of cognitive aging trajectories across individuals. Preliminary analyses of brain tissues from this cohort also show highly variable degrees of neuropathology. Future work will tie together behavioral trajectories with brain pathology and provide a window into the factors that predict age-related cognitive decline.

Research paper thumbnail of Age-related decline in executive function as a hallmark of cognitive ageing in primates: an overview of cognitive and neurobiological studies

Philosophical Transactions of the Royal Society B: Biological Sciences

Executive function (EF) is a complex construct that reflects multiple higher-order cognitive proc... more Executive function (EF) is a complex construct that reflects multiple higher-order cognitive processes such as planning, updating, inhibiting and set-shifting. Decline in these functions is a hallmark of cognitive ageing in humans, and age differences and changes in EF correlate with age-related differences and changes in association cortices, particularly the prefrontal areas. Here, we review evidence for age-related decline in EF and associated neurobiological changes in prosimians, New World and Old World monkeys, apes and humans. While EF declines with age in all primate species studied, the relationship of this decline with age-related alterations in the prefrontal cortex remains unclear, owing to the scarcity of neurobiological studies focusing on the ageing brain in most primate species. In addition, the influence of sex, vascular and metabolic risk, and hormonal status has rarely been considered. We outline several methodological limitations and challenges with the goal of p...

Research paper thumbnail of Sex differences in cognitive aging: a 4-year longitudinal study in marmosets

Research paper thumbnail of Nonhuman primates at the intersection of aging biology, chronic disease, and health: An introduction to the American journal of primatology special issue on aging, cognitive decline, and neuropathology in nonhuman primates

American Journal of Primatology

Research paper thumbnail of Robustness of sex-differences in functional connectivity over time in middle-aged marmosets

Scientific Reports

Nonhuman primates (NHPs) are an essential research model for gaining a comprehensive understandin... more Nonhuman primates (NHPs) are an essential research model for gaining a comprehensive understanding of the neural mechanisms of neurocognitive aging in our own species. In the present study, we used resting state functional connectivity (rsFC) to investigate the relationship between prefrontal cortical and striatal neural interactions, and cognitive flexibility, in unanaesthetized common marmosets (Callithrix jacchus) at two time points during late middle age (8 months apart, similar to a span of 5–6 years in humans). Based on our previous findings, we also determine the reproducibility of connectivity measures over the course of 8 months, particularly previously observed sex differences in rsFC. Male marmosets exhibited remarkably similar patterns of stronger functional connectivity relative to females and greater cognitive flexibility between the two imaging time points. Network analysis revealed that the consistent sex differences in connectivity and related cognitive associations...

Research paper thumbnail of Baseline cortisol levels and social behavior differ as a function of handedness in marmosets ( Callithrix jacchus )

American Journal of Primatology

Research paper thumbnail of One-year change in cognitive flexibility and fine motor function in middle-aged male and female marmosets (Callithrix jacchus )

American Journal of Primatology

Research paper thumbnail of Adverse effects of aromatase inhibition on the brain and behavior in a non-human primate

The Journal of Neuroscience

Breast cancer patients using aromatase inhibitors (AIs) as an adjuvant therapy often report side ... more 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.

Research paper thumbnail of Haptic Perception in Baboons <i>(Papio papio</i><i>)</i>: Preliminary Evidence for Lateralization in Accuracy and Exploration Time

Folia Primatologica

Two baboons performed 2 types of haptic discrimination of three-dimensional object pairs, by usin... more Two baboons performed 2 types of haptic discrimination of three-dimensional object pairs, by using the right and left hands in the same number of trials. One task focused on the discrimination of the objects’ shape, another on the convexity or concavity of the objects. It was found that the left was better than the right hand to discriminate the shape of objects. Regardless of the task, objects were also explored longer with the left than with the right hand. It is suggested that these hand differences are congruent with the hypothesis of an advantage of the right hemisphere in monkeys for haptic perception.Copyright © 1995 S. Karger AG, Basel

Research paper thumbnail of Subject index to volume one

Pulmonary Pharmacology

Abdominal surgery, catheterization and bladder drainage after, 32. 33 Abdominal wall defects. ant... more Abdominal surgery, catheterization and bladder drainage after, 32. 33 Abdominal wall defects. anterior, 147-53 Ablation in cervical intraepithelial neoplasia. I39 endometrial, hysterosurgical techniques in, 43-4 Adenectomy with pituitary prolactinomas, 88 Adenomas, pituitary, infertility with, 88-90 Adrenal gland, hyperandrogenisation and the, 210 p-Adrenoceptor agonists, see Beta agonists Aged, stress incontinence, 104 Agenesis. vulval. 154-7 AIDS and AIDS-related complex in babies, 79, see also HIV Alphafetoprotein in anterior abdominal wall defects, 149 Amenorrhoea, oral contraceptives and. 237 Amniotic fluid, infection, 68,679 Amniotic graft in vulva1 agenesis. 156-7 Amniotomy in induction of labour, 218. 219 Ampicillin in pregnancy. 49 Ampullary mucosa of fallopian tubes, endoscopy, 229-33 Anaemia, congenital pure red cell, 176-X Analgesia, regional, fluid use during. 36-7 Analgesics, teratogenicity.

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

Neuroscience, 2016

Menopausal women often suffer from hot flashes and sleep disturbances that significantly impact t... more Menopausal women often suffer from hot flashes and sleep disturbances that significantly impact their quality of life. Both human and animal studies suggest that loss of estrogens during menopause contribute to these symptoms. In the female rat, both core body temperature (CBT) and sleep are sensitive to 17β-estradiol (E2) levels, but important differences between the rat and the human patterns limit the interpretation of the results. The sleep and thermoregulation of the common marmoset (Callithrix jacchus) more closely resemble human patterns. However, no study to date has examined whether E2 influences sleep and thermoregulation in this species. The main goal of the present study was to investigate the suitability of the ovariectomized (OVX) marmoset for studying two major menopausal symptoms experienced by women, sleep disturbance and thermodysregulation. Two middle-aged OVX marmosets (6years old) were implanted with a telemeter that records electroencephalograms (EEG), electromyograms (EMG), and CBT. Sleep patterns and CBT were recorded under baseline, two E2 replacement (6 and 12μg/kg/day, p.o.) conditions and two E2 withdrawal conditions. Relative to both baseline and withdrawal, high E2 replacement was associated with lower nighttime CBT. In addition, fewer nighttime arousals were observed under low E2 replacement compared to baseline. Higher delta power was observed under both E2 replacement conditions suggesting enhanced sleep quality. These preliminary results suggest that E2 modulates sleep and thermoregulation in the OVX marmoset, making it a promising model for studying menopausal symptoms.

Research paper thumbnail of Nonhuman Primate Models of Cognitive Aging

Animal Models of Human Cognitive Aging, 2008

Nonhuman primates are indispensable for the study of aging processes. Like other animals, they pe... more Nonhuman primates are indispensable for the study of aging processes. Like other animals, they permit us to observe the effects of age in the absence of the confounds inherent in studies of human beings. Additionally, because they are phylogenetically close to humans and possess certain uniquely primate morphological, endocrine, behavioral, and cognitive traits, they can provide data uniquely relevant to human aging. Among nonhuman primates, the rhesus monkey is by far the most widely studied in the context of aging, as verified in the large number of reviews that have summarized the studies on this species. To date, however, there is no published overview of the many other species of nonhuman primates in which age-related changes have been studied. This chapter is intended to fill that gap. Thus, we discuss results from a wide variety of prosimian, monkey, and ape species, ranging from the mouse lemur to the great apes. We include species about which a great deal is known as well as those, such as the gorilla and chimpanzee, on which only one or two studies have been conducted. For each species or group of species, we describe what is known about age-related changes in cognition, in the brain, and in patterns of reproductive senescence. We conclude that, although studies on the rhesus monkeys have provided the greatest depth of knowledge about cognitive aging processes, the many other primate species, with their wide variety of reproductive, morphological, and behavioral adaptations, can shed new light on the factors underlying age-related cognitive changes in our own species.

Research paper thumbnail of Neurocognitive effects of estrogens across the adult lifespan in nonhuman primates: State of knowledge and new perspectives

Hormones and behavior, Jan 8, 2015

This review discusses the unique contribution of nonhuman primate research to our understanding o... more This review discusses the unique contribution of nonhuman primate research to our understanding of the neurocognitive effects of estrogens throughout the adult lifespan in females. Mounting evidence indicates that estrogens affect many aspects of hippocampal, prefrontal and cholinergic function in the primate brain and the underlying mechanisms are beginning to be elucidated. In addition, estrogens may also influence cognitive function indirectly, via the modulation of other systems that impact cognition. We will focus on the effects of estrogens on sleep and emphasize the need for primate models to better understand these complex interactions. Continued research with nonhuman primates is essential for the development of therapies that are optimal for the maintenance of women's cognitive health throughout the lifespan.

Research paper thumbnail of Chapter 13. Tactile exploration in nonhuman primates

Advances in Consciousness Research, 2003

Research paper thumbnail of ‘SERM’ fulfills its promise

Trends in Endocrinology & Metabolism, 2003

Research paper thumbnail of Short-term testosterone manipulations do not affect cognition or motor function but differentially modulate emotions in young and older male rhesus monkeys

Hormones and behavior, 2014

Human aging is characterized by declines in cognition and fine motor function as well as improved... more Human aging is characterized by declines in cognition and fine motor function as well as improved emotional regulation. In men, declining levels of testosterone (T) with age have been implicated in the development of these age-related changes. However, studies examining the effects of T replacement on cognition, emotion and fine motor function in older men have not provided consistent results. Rhesus monkeys (Macaca mulatta) are excellent models for human cognitive aging and may provide novel insights on this issue. We tested 10 aged intact male rhesus monkeys (mean age=19, range 15-25) on a battery of cognitive, motor and emotional tasks at baseline and under low or high T experimental conditions. Their performance was compared to that of 6 young males previously tested in the same paradigm (Lacreuse et al., 2009; Lacreuse et al., 2010). Following a 4-week baseline testing period, monkeys were treated with a gonadotropin releasing hormone agonist (Depot Lupron, 200 μg/kg) to suppre...

Research paper thumbnail of No effect of different estrogen receptor ligands on cognition in adult female monkeys

Physiology & behavior, Jan 2, 2009

Many studies in women and animal models suggest that estrogens affect cognitive function. Yet, th... more Many studies in women and animal models suggest that estrogens affect cognitive function. Yet, the mechanisms by which estrogens may impact cognition remain unclear. The goal of the present study was to assess the effects of different estrogen receptor (ER) ligands on cognitive function in adult ovariectomized female rhesus monkeys. The monkeys were tested for 6 weeks on a battery of memory and attentional tasks administered on a touchscreen: the object, face, and spatial versions of the Delayed Recognition Span Test (DRST) and a Visual Search task. Following a 2-week baseline period with oil vehicle treatment, monkeys were randomly assigned to one of 3 treatment groups: estradiol benzoate (EB), selective ERbeta agonist (diarylpropionitrile DPN) or selective ER modulator tamoxifen (TAM). In each treatment group, monkeys received oil vehicle for 2 weeks and the drug for 2 weeks, in a cross-over design. After a 4-week washout, a subset of monkeys was re-tested on the battery when trea...

Research paper thumbnail of Fluctuations in spatial recognition memory across the menstrual cycle in female rhesus monkeys

Psychoneuroendocrinology, 2001

Findings are inconsistent regarding whether women&#39;s cognitive performance fluctuates acro... more Findings are inconsistent regarding whether women&#39;s cognitive performance fluctuates across phases of the menstrual cycle, but differences in methodology and the use of reported cycle phase rather than precise hormonal measures may underlie these disparities. Studies in monkeys may help resolve these discrepant findings, since hormonal status can be reliably determined. We tested four young (5-7 years old) female rhesus monkeys daily during one entire menstrual cycle on three cognitive tasks displayed on a computerized touch-screen system: a Matching to Sample task with a 30 s delay (MTS-30s), a Matching to Sample task without delay (MTS-no delay) and the spatial condition of the Delayed Recognition Span Test (spatial-DRST). Blood samples were collected at specific time intervals throughout the cycle and assayed for estradiol and progesterone in order to identify hormonal status. There was a nonsignificant trend for the MTS-30s scores to be better during the follicular and luteal phases, when estradiol levels were low, than during the peri-ovulatory phase, when estradiol levels were at their highest. MTS-no delay performance did not vary as a function of hormonal status. Spatial-DRST scores were significantly better during the follicular and luteal phases than during the peri-ovulatory phase of the cycle. These data in the female rhesus monkey support the hypothesis that spatial memory performance is sensitive to estradiol variations across the menstrual cycle, with better performance associated with low estradiol levels.

Research paper thumbnail of Effects of testosterone on attention and memory for emotional stimuli in male rhesus monkeys

Psychoneuroendocrinology, 2012

Increasing evidence in humans and other animals suggests that testosterone (T) plays an important... more Increasing evidence in humans and other animals suggests that testosterone (T) plays an important role in modulating emotion. We previously reported that T treatment in rhesus monkeys undergoing chemically induced hypogonadism results in increased watching time of videos depicting fights between unfamiliar conspecifics (Lacreuse et al., 2010). In the current study, we aimed to further investigate the effect of T manipulations on attention and memory for emotional stimuli in male rhesus monkeys. Six males (7 years old) were administered Depot Lupron to suppress endogenous T levels and treated with either testosterone enanthate (TE, 5 mg/kg) or oil, before crossing over to the alternate treatment. Animals were tested for 16 weeks on two computerized touchscreen tasks with both social and nonsocial emotional and neutral stimuli. The Dot-Probe task was used to measure attention, and the Delayed-Non-Matching-to-Sample task with a 1 s delay (DNMS) was used to measure recognition memory for these stimuli. Performance on the two tasks was examined during each of four month-long phases: Baseline, Lupron alone, Lupron + TE and Lupron + oil. It was predicted that T administration would lead to increased attention to negative social stimuli (i.e., negative facial expressions of unfamiliar conspecifics) and would improve memory for such stimuli. We found no evidence to support these predictions. In the Dot-Probe task, an attentional bias towards negative social stimuli was observed at baseline, but T treatment did not enhance this bias. Instead, monkeys had faster response times when treated with T compared to oil, independently of the emotional valence or social relevance of stimuli, perhaps reflecting an enhancing effect of T on reward sensitivity or general arousal. In the DNMS, animals had better memory for nonsocial compared to social stimuli and showed the poorest performance in the recognition of positive facial expressions. However, T did not affect performance on the task. Thus, even though monkeys were sensitive to the social relevance and emotional valence of the stimuli in the two tasks, T manipulations had no effect on attention or memory for these stimuli. Because habituation to the stimuli may have mitigated the effect of treatment in the attentional task, we suggest that T may increase attentional biases to negative social stimuli only during early exposure to the stimuli with

Research paper thumbnail of Effect of menstrual cycle on resting brain metabolism in female rhesus monkeys

NeuroReport, 2008

Little is known about the effects of the menstrual cycle on brain activity in primates. Here, we ... more Little is known about the effects of the menstrual cycle on brain activity in primates. Here, we use 18F-fluorodeoxyglucose positron emission tomography to monitor changes in resting brain glucose metabolism across the menstrual cycle in female rhesus monkeys. Results showed greater activity in right lateral orbitofrontal cortex, a region involved in processing negatively valenced emotional stimuli, in the follicular compared with luteal phase. Estradiol levels were negatively correlated with activity in cortical and brainstem regions involved in emotional processing, and positively correlated with activity in areas involved in cognitive control and emotion regulation. In summary, the data suggest that in primates, fluctuations of ovarian hormones across the menstrual cycle influence activity in brain areas involved in emotion and its regulation.

Research paper thumbnail of The marmoset as an important primate model for longitudinal studies of neurocognitive aging

American Journal of Primatology

Age-related cognitive decline has been extensively studied in humans, but the majority of researc... more Age-related cognitive decline has been extensively studied in humans, but the majority of research designs are cross-sectional and compare across younger and older adults. Longitudinal studies are necessary to capture variability in cognitive aging trajectories but are difficult to carry out in humans and long-lived nonhuman primates. Marmosets are an ideal primate model for neurocognitive aging as their naturally short lifespan facilitates longitudinal designs. In a longitudinal study of marmosets tested on reversal learning starting in middle-age, we found that, on average, the group of marmosets declined in cognitive performance around 8 years of age. However, we found highly variable patterns of cognitive aging trajectories across individuals. Preliminary analyses of brain tissues from this cohort also show highly variable degrees of neuropathology. Future work will tie together behavioral trajectories with brain pathology and provide a window into the factors that predict age-related cognitive decline.

Research paper thumbnail of Age-related decline in executive function as a hallmark of cognitive ageing in primates: an overview of cognitive and neurobiological studies

Philosophical Transactions of the Royal Society B: Biological Sciences

Executive function (EF) is a complex construct that reflects multiple higher-order cognitive proc... more Executive function (EF) is a complex construct that reflects multiple higher-order cognitive processes such as planning, updating, inhibiting and set-shifting. Decline in these functions is a hallmark of cognitive ageing in humans, and age differences and changes in EF correlate with age-related differences and changes in association cortices, particularly the prefrontal areas. Here, we review evidence for age-related decline in EF and associated neurobiological changes in prosimians, New World and Old World monkeys, apes and humans. While EF declines with age in all primate species studied, the relationship of this decline with age-related alterations in the prefrontal cortex remains unclear, owing to the scarcity of neurobiological studies focusing on the ageing brain in most primate species. In addition, the influence of sex, vascular and metabolic risk, and hormonal status has rarely been considered. We outline several methodological limitations and challenges with the goal of p...

Research paper thumbnail of Sex differences in cognitive aging: a 4-year longitudinal study in marmosets

Research paper thumbnail of Nonhuman primates at the intersection of aging biology, chronic disease, and health: An introduction to the American journal of primatology special issue on aging, cognitive decline, and neuropathology in nonhuman primates

American Journal of Primatology

Research paper thumbnail of Robustness of sex-differences in functional connectivity over time in middle-aged marmosets

Scientific Reports

Nonhuman primates (NHPs) are an essential research model for gaining a comprehensive understandin... more Nonhuman primates (NHPs) are an essential research model for gaining a comprehensive understanding of the neural mechanisms of neurocognitive aging in our own species. In the present study, we used resting state functional connectivity (rsFC) to investigate the relationship between prefrontal cortical and striatal neural interactions, and cognitive flexibility, in unanaesthetized common marmosets (Callithrix jacchus) at two time points during late middle age (8 months apart, similar to a span of 5–6 years in humans). Based on our previous findings, we also determine the reproducibility of connectivity measures over the course of 8 months, particularly previously observed sex differences in rsFC. Male marmosets exhibited remarkably similar patterns of stronger functional connectivity relative to females and greater cognitive flexibility between the two imaging time points. Network analysis revealed that the consistent sex differences in connectivity and related cognitive associations...

Research paper thumbnail of Baseline cortisol levels and social behavior differ as a function of handedness in marmosets ( Callithrix jacchus )

American Journal of Primatology

Research paper thumbnail of One-year change in cognitive flexibility and fine motor function in middle-aged male and female marmosets (Callithrix jacchus )

American Journal of Primatology

Research paper thumbnail of Adverse effects of aromatase inhibition on the brain and behavior in a non-human primate

The Journal of Neuroscience

Breast cancer patients using aromatase inhibitors (AIs) as an adjuvant therapy often report side ... more 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.

Research paper thumbnail of Haptic Perception in Baboons <i>(Papio papio</i><i>)</i>: Preliminary Evidence for Lateralization in Accuracy and Exploration Time

Folia Primatologica

Two baboons performed 2 types of haptic discrimination of three-dimensional object pairs, by usin... more Two baboons performed 2 types of haptic discrimination of three-dimensional object pairs, by using the right and left hands in the same number of trials. One task focused on the discrimination of the objects’ shape, another on the convexity or concavity of the objects. It was found that the left was better than the right hand to discriminate the shape of objects. Regardless of the task, objects were also explored longer with the left than with the right hand. It is suggested that these hand differences are congruent with the hypothesis of an advantage of the right hemisphere in monkeys for haptic perception.Copyright © 1995 S. Karger AG, Basel

Research paper thumbnail of Subject index to volume one

Pulmonary Pharmacology

Abdominal surgery, catheterization and bladder drainage after, 32. 33 Abdominal wall defects. ant... more Abdominal surgery, catheterization and bladder drainage after, 32. 33 Abdominal wall defects. anterior, 147-53 Ablation in cervical intraepithelial neoplasia. I39 endometrial, hysterosurgical techniques in, 43-4 Adenectomy with pituitary prolactinomas, 88 Adenomas, pituitary, infertility with, 88-90 Adrenal gland, hyperandrogenisation and the, 210 p-Adrenoceptor agonists, see Beta agonists Aged, stress incontinence, 104 Agenesis. vulval. 154-7 AIDS and AIDS-related complex in babies, 79, see also HIV Alphafetoprotein in anterior abdominal wall defects, 149 Amenorrhoea, oral contraceptives and. 237 Amniotic fluid, infection, 68,679 Amniotic graft in vulva1 agenesis. 156-7 Amniotomy in induction of labour, 218. 219 Ampicillin in pregnancy. 49 Ampullary mucosa of fallopian tubes, endoscopy, 229-33 Anaemia, congenital pure red cell, 176-X Analgesia, regional, fluid use during. 36-7 Analgesics, teratogenicity.

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

Neuroscience, 2016

Menopausal women often suffer from hot flashes and sleep disturbances that significantly impact t... more Menopausal women often suffer from hot flashes and sleep disturbances that significantly impact their quality of life. Both human and animal studies suggest that loss of estrogens during menopause contribute to these symptoms. In the female rat, both core body temperature (CBT) and sleep are sensitive to 17β-estradiol (E2) levels, but important differences between the rat and the human patterns limit the interpretation of the results. The sleep and thermoregulation of the common marmoset (Callithrix jacchus) more closely resemble human patterns. However, no study to date has examined whether E2 influences sleep and thermoregulation in this species. The main goal of the present study was to investigate the suitability of the ovariectomized (OVX) marmoset for studying two major menopausal symptoms experienced by women, sleep disturbance and thermodysregulation. Two middle-aged OVX marmosets (6years old) were implanted with a telemeter that records electroencephalograms (EEG), electromyograms (EMG), and CBT. Sleep patterns and CBT were recorded under baseline, two E2 replacement (6 and 12μg/kg/day, p.o.) conditions and two E2 withdrawal conditions. Relative to both baseline and withdrawal, high E2 replacement was associated with lower nighttime CBT. In addition, fewer nighttime arousals were observed under low E2 replacement compared to baseline. Higher delta power was observed under both E2 replacement conditions suggesting enhanced sleep quality. These preliminary results suggest that E2 modulates sleep and thermoregulation in the OVX marmoset, making it a promising model for studying menopausal symptoms.

Research paper thumbnail of Nonhuman Primate Models of Cognitive Aging

Animal Models of Human Cognitive Aging, 2008

Nonhuman primates are indispensable for the study of aging processes. Like other animals, they pe... more Nonhuman primates are indispensable for the study of aging processes. Like other animals, they permit us to observe the effects of age in the absence of the confounds inherent in studies of human beings. Additionally, because they are phylogenetically close to humans and possess certain uniquely primate morphological, endocrine, behavioral, and cognitive traits, they can provide data uniquely relevant to human aging. Among nonhuman primates, the rhesus monkey is by far the most widely studied in the context of aging, as verified in the large number of reviews that have summarized the studies on this species. To date, however, there is no published overview of the many other species of nonhuman primates in which age-related changes have been studied. This chapter is intended to fill that gap. Thus, we discuss results from a wide variety of prosimian, monkey, and ape species, ranging from the mouse lemur to the great apes. We include species about which a great deal is known as well as those, such as the gorilla and chimpanzee, on which only one or two studies have been conducted. For each species or group of species, we describe what is known about age-related changes in cognition, in the brain, and in patterns of reproductive senescence. We conclude that, although studies on the rhesus monkeys have provided the greatest depth of knowledge about cognitive aging processes, the many other primate species, with their wide variety of reproductive, morphological, and behavioral adaptations, can shed new light on the factors underlying age-related cognitive changes in our own species.

Research paper thumbnail of Neurocognitive effects of estrogens across the adult lifespan in nonhuman primates: State of knowledge and new perspectives

Hormones and behavior, Jan 8, 2015

This review discusses the unique contribution of nonhuman primate research to our understanding o... more This review discusses the unique contribution of nonhuman primate research to our understanding of the neurocognitive effects of estrogens throughout the adult lifespan in females. Mounting evidence indicates that estrogens affect many aspects of hippocampal, prefrontal and cholinergic function in the primate brain and the underlying mechanisms are beginning to be elucidated. In addition, estrogens may also influence cognitive function indirectly, via the modulation of other systems that impact cognition. We will focus on the effects of estrogens on sleep and emphasize the need for primate models to better understand these complex interactions. Continued research with nonhuman primates is essential for the development of therapies that are optimal for the maintenance of women's cognitive health throughout the lifespan.

Research paper thumbnail of Chapter 13. Tactile exploration in nonhuman primates

Advances in Consciousness Research, 2003

Research paper thumbnail of ‘SERM’ fulfills its promise

Trends in Endocrinology & Metabolism, 2003

Research paper thumbnail of Short-term testosterone manipulations do not affect cognition or motor function but differentially modulate emotions in young and older male rhesus monkeys

Hormones and behavior, 2014

Human aging is characterized by declines in cognition and fine motor function as well as improved... more Human aging is characterized by declines in cognition and fine motor function as well as improved emotional regulation. In men, declining levels of testosterone (T) with age have been implicated in the development of these age-related changes. However, studies examining the effects of T replacement on cognition, emotion and fine motor function in older men have not provided consistent results. Rhesus monkeys (Macaca mulatta) are excellent models for human cognitive aging and may provide novel insights on this issue. We tested 10 aged intact male rhesus monkeys (mean age=19, range 15-25) on a battery of cognitive, motor and emotional tasks at baseline and under low or high T experimental conditions. Their performance was compared to that of 6 young males previously tested in the same paradigm (Lacreuse et al., 2009; Lacreuse et al., 2010). Following a 4-week baseline testing period, monkeys were treated with a gonadotropin releasing hormone agonist (Depot Lupron, 200 μg/kg) to suppre...

Research paper thumbnail of No effect of different estrogen receptor ligands on cognition in adult female monkeys

Physiology & behavior, Jan 2, 2009

Many studies in women and animal models suggest that estrogens affect cognitive function. Yet, th... more Many studies in women and animal models suggest that estrogens affect cognitive function. Yet, the mechanisms by which estrogens may impact cognition remain unclear. The goal of the present study was to assess the effects of different estrogen receptor (ER) ligands on cognitive function in adult ovariectomized female rhesus monkeys. The monkeys were tested for 6 weeks on a battery of memory and attentional tasks administered on a touchscreen: the object, face, and spatial versions of the Delayed Recognition Span Test (DRST) and a Visual Search task. Following a 2-week baseline period with oil vehicle treatment, monkeys were randomly assigned to one of 3 treatment groups: estradiol benzoate (EB), selective ERbeta agonist (diarylpropionitrile DPN) or selective ER modulator tamoxifen (TAM). In each treatment group, monkeys received oil vehicle for 2 weeks and the drug for 2 weeks, in a cross-over design. After a 4-week washout, a subset of monkeys was re-tested on the battery when trea...

Research paper thumbnail of Fluctuations in spatial recognition memory across the menstrual cycle in female rhesus monkeys

Psychoneuroendocrinology, 2001

Findings are inconsistent regarding whether women&#39;s cognitive performance fluctuates acro... more Findings are inconsistent regarding whether women&#39;s cognitive performance fluctuates across phases of the menstrual cycle, but differences in methodology and the use of reported cycle phase rather than precise hormonal measures may underlie these disparities. Studies in monkeys may help resolve these discrepant findings, since hormonal status can be reliably determined. We tested four young (5-7 years old) female rhesus monkeys daily during one entire menstrual cycle on three cognitive tasks displayed on a computerized touch-screen system: a Matching to Sample task with a 30 s delay (MTS-30s), a Matching to Sample task without delay (MTS-no delay) and the spatial condition of the Delayed Recognition Span Test (spatial-DRST). Blood samples were collected at specific time intervals throughout the cycle and assayed for estradiol and progesterone in order to identify hormonal status. There was a nonsignificant trend for the MTS-30s scores to be better during the follicular and luteal phases, when estradiol levels were low, than during the peri-ovulatory phase, when estradiol levels were at their highest. MTS-no delay performance did not vary as a function of hormonal status. Spatial-DRST scores were significantly better during the follicular and luteal phases than during the peri-ovulatory phase of the cycle. These data in the female rhesus monkey support the hypothesis that spatial memory performance is sensitive to estradiol variations across the menstrual cycle, with better performance associated with low estradiol levels.

Research paper thumbnail of Effects of testosterone on attention and memory for emotional stimuli in male rhesus monkeys

Psychoneuroendocrinology, 2012

Increasing evidence in humans and other animals suggests that testosterone (T) plays an important... more Increasing evidence in humans and other animals suggests that testosterone (T) plays an important role in modulating emotion. We previously reported that T treatment in rhesus monkeys undergoing chemically induced hypogonadism results in increased watching time of videos depicting fights between unfamiliar conspecifics (Lacreuse et al., 2010). In the current study, we aimed to further investigate the effect of T manipulations on attention and memory for emotional stimuli in male rhesus monkeys. Six males (7 years old) were administered Depot Lupron to suppress endogenous T levels and treated with either testosterone enanthate (TE, 5 mg/kg) or oil, before crossing over to the alternate treatment. Animals were tested for 16 weeks on two computerized touchscreen tasks with both social and nonsocial emotional and neutral stimuli. The Dot-Probe task was used to measure attention, and the Delayed-Non-Matching-to-Sample task with a 1 s delay (DNMS) was used to measure recognition memory for these stimuli. Performance on the two tasks was examined during each of four month-long phases: Baseline, Lupron alone, Lupron + TE and Lupron + oil. It was predicted that T administration would lead to increased attention to negative social stimuli (i.e., negative facial expressions of unfamiliar conspecifics) and would improve memory for such stimuli. We found no evidence to support these predictions. In the Dot-Probe task, an attentional bias towards negative social stimuli was observed at baseline, but T treatment did not enhance this bias. Instead, monkeys had faster response times when treated with T compared to oil, independently of the emotional valence or social relevance of stimuli, perhaps reflecting an enhancing effect of T on reward sensitivity or general arousal. In the DNMS, animals had better memory for nonsocial compared to social stimuli and showed the poorest performance in the recognition of positive facial expressions. However, T did not affect performance on the task. Thus, even though monkeys were sensitive to the social relevance and emotional valence of the stimuli in the two tasks, T manipulations had no effect on attention or memory for these stimuli. Because habituation to the stimuli may have mitigated the effect of treatment in the attentional task, we suggest that T may increase attentional biases to negative social stimuli only during early exposure to the stimuli with