Carol A Shively

Carol A Shively
Wake Forest School of Medicine · Section on Comparative Medicine

Ph.D.

About

219
Publications
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Publications

Publications (219)
Article
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Dietary composition is associated with the differential prevalence of psychiatric disorders; the Western diet confers increased risk, while the Mediterranean diet appears to reduce risk. In nonhuman primates, anxiety-like behaviors and social isolation have been linked to both Western diet consumption and increased inflammatory disease risk, and re...
Article
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Introduction: Age-related neuropathology associated with sporadic Alzheimer's disease (AD) often develops well before the onset of symptoms. Given AD's long preclinical period, translational models are needed to identify early signatures of pathological decline. Methods: Using structural magnetic resonance imaging and cognitive assessments, we e...
Article
Chronic psychosocial stress is associated with increased risk of many chronic diseases including type 2 diabetes mellitus. However, it is difficult to establish a causal relationship between stress and diabetes in human studies because stressors often are self-reported and may be distant in time from metabolic consequences. Macaques are useful mode...
Article
Synaptic molecular characterization is limited for Alzheimer’s disease (AD). Our newly invented mass cytometry–based method, synaptometry by time of flight (SynTOF), was used to measure 38 antibody probes in approximately 17 million single-synapse events from human brains without pathologic change or with pure AD or Lewy body disease (LBD), nonhuma...
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Age-related changes in DNA methylation are potent regulators of gene expression and may in part explain the onset of disease and disability. Vervet monkeys are a well-described model of neurocognitive and physical aging. Like humans, gait speed declines with age in vervets, and variability in gait speed in older animals is associated with age-relat...
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Ovarian dysfunction increases risk for chronic diseases of aging including cardiovascular disease, depression, cognitive impairment, and bone and muscle loss which promote frailty. Psychosocial stress disrupts ovarian function and recent observations suggest that Western diet may also. Determination of causal relationships among diet, psychosocial...
Article
Microtubule (MT) integrity is critical for cell function and viability. Abnormal MT stability is commonly attributed to hyperphosphorylation of the MT‐associated protein, tau. However, the time course of MT instability in disease progression remains unknown. In vivo MT imaging offers an opportunity to gain critical information on MT changes in rela...
Article
Mounting evidence suggests that diet may influence risk for cognitive impairment and neurodegenerative disease, including Alzheimer’s disease. Nonhuman primates are important models of cognitive aging and Alzheimer’s disease‐like neuropathology given their complex central nervous systems and susceptibility to diet‐induced diseases. Diffusion magnet...
Article
Age‐related neurodegeneration characteristic of late‐onset Alzheimer’s disease (LOAD) begins in middle age, well before symptoms. Therefore, translational models to identify modifiable risk factors in middle‐age are needed to understand the etiology and identify early therapeutic targets for intervention. Vervet monkeys (Chlorocebus aethiops sabaeu...
Article
Microtubule (MT) integrity is critical for cell function and viability. Abnormal MT‐stability in AD is commonly attributed to hyperphosphorylation of the MT‐associated protein, tau. However, the time course of MT instability in disease progression remains unknown. In vivo MT imaging offers an opportunity to gain critical information on MT changes i...
Article
Mitochondrial dysfunction is evident in diseases affecting cognition and metabolism such as Alzheimer's disease and type 2 diabetes. Human studies of brain mitochondrial function are limited to post-mortem tissue, preventing the assessment of bioenergetics by respirometry. Here, we investigated the effect of two diets on mitochondrial bioenergetics...
Article
Western diets increase the prevalence of chronic diseases. Peripheral blood monocytes, macrophage precursors and important mediators of innate immunity and inflammation, are sensitive to the environment and may be a critical pathway linking diet to disease. We determined effects of 15 months of Western or Mediterranean diet on monocyte polarization...
Article
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Dietary changes associated with industrialization increase the prevalence of chronic diseases, such as obesity, type II diabetes, and cardiovascular disease. This relationship is often attributed to an ‘evolutionary mismatch’ between human physiology and modern nutritional environments. Western diets enriched with foods that were scarce throughout...
Article
AMP-activated protein kinase (AMPK) is a molecular sensor that is critical for the maintenance of cellular energy homeostasis, disruption of which has been indicated in multiple neurodegenerative diseases including Alzheimer's disease (AD). Mammalian AMPK is a heterotrimeric complex and its enzymatic α subunit exists in two isoforms: AMPKα1 and AMP...
Article
Aging across the Primate Order is poorly understood because ages of individuals are often unknown, there is a dearth of aged animals available for study, and because aging is best characterized by longitudinal studies which are difficult in long-lived species. The human population is aging rapidly, and advanced age is a primary risk factor for seve...
Preprint
Synaptic molecular characterization is limited for Alzheimers disease (AD). We used mass cytometry to quantify 38 probes in approximately 17 million single synaptic events from human brains without pathologic change or with pure AD or Lewy body disease (LBD), non-human primates (NHP), and PS/APP mice. Synaptic molecular integrity in humans and NHP...
Article
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Background The objective of this study was to increase understanding of the complex interactions between diet, obesity, and the gut microbiome of adult female non-human primates (NHPs). Subjects consumed either a Western (n=15) or Mediterranean (n=14) diet designed to represent human dietary patterns for 31 months. Body composition was determined u...
Article
Age‐related neurodegeneration characteristic of late‐onset Alzheimer's disease (LOAD) begins in middle age, well before symptoms. Translational models to identify modifiable risk factors are needed to understand etiology and identify therapeutic targets. Here, we outline the evidence supporting the vervet monkey (Chlorocebus aethiops sabaeus) as a...
Article
Full-text available
Dual declines in gait speed and cognitive performance are associated with increased risk of developing dementia. Characterizing the patterns of such impairments therefore is paramount to distinguishing healthy from pathological aging. Nonhuman primates such as vervet/African green monkeys (Chlorocebus aethiops sabaeus) are important models of human...
Article
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Adolescent depression is a common and serious mental disorder with unique characteristics that are distinct from adult depression. The adult non-human primate stress-induced model of depressive-like behavior is an excellent model for the study of mechanisms; however, an adolescent nonhuman primate model is still lacking. Ten male adolescent cynomol...
Article
Full-text available
Age-related neurodegeneration associated with Alzheimer’s (AD) disease begins in middle age, well before the onset of symptoms. Therefore, translational models to identify modifiable risk factors in middle-age are needed to understand etiology and identify therapeutic targets. Vervet monkeys (Chlorocebus aethiops sabaeus), like humans, naturally de...
Article
Full-text available
Diet may influence the risk for cognitive decline and neurodegenerative disorders, including Alzheimer’s disease (AD), but these relationships are difficult to study in humans. Cynomolgus macaques (Macaca fascicularis) are appropriate models for investigations of diet effects on the brain because, like humans, they are omnivorous, have complex cent...
Article
Full-text available
Introduction: Associations between diet, psychosocial stress, and neurodegenerative disease, including Alzheimer's disease (AD), have been reported, but causal relationships are difficult to determine in human studies. Methods: We used structural magnetic resonance imaging in a well-validated non-human primate model of AD-like neuropathology to...
Article
Associations between diet, cognitive decline and neurodegenerative disease, including Alzheimer’s Disease (AD), have been reported, but whether these relationships are causal is difficult to determine in human studies. Cynomolgus macaques (Macaca fascicularis), like humans, are omnivorous, have complex central nervous systems, and are susceptible t...
Article
Full-text available
Persistent psychological stress increases the risk of many chronic diseases of aging. Little progress has been made to effectively reduce stress responses or mitigate stress effects suggesting a need for better understanding of factors that influence stress responses. Limited evidence suggests that diet may be a factor in modifying the effects of s...
Preprint
Full-text available
Persistent psychological stress increases the risk of many chronic diseases of aging. Little progress has been made to effectively reduce stress responses or mitigate stress effects suggesting a need for better understanding of factors that influence stress responses. Limited evidence suggests that diet may be a factor in modifying the effects of s...
Preprint
Full-text available
INTRODUCTION Associations between diet, psychosocial stress, and neurodegenerative disease, including Alzheimer’s disease (AD), have been reported, but causal relationships are difficult to determine in human studies. METHODS We used structural magnetic resonance imaging in a well-validated nonhuman primate model of AD-like neuropathology to exami...
Article
Objectives Poor diet and obesity often go hand-in-hand and are difficult to discern which variable is the major driver of the gut microbiome. The objective of this study was to determine the impact of obesity within dietary exposures on the gut microbiome and metabolic parameters using a non-human primate model. Methods Female M. fasicularis monke...
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The social environment, both in early life and adulthood, is one of the strongest predictors of morbidity and mortality risk in humans. Evidence from long-term studies of other social mammals indicates that this relationship is similar across many species. In addition, experimental studies show that social interactions can causally alter animal phy...
Preprint
Full-text available
Dietary changes associated with industrialization substantially increase the prevalence of chronic diseases, such as obesity, type II diabetes, and cardiovascular disease, which are major contributors to the public health burden. The high prevalence of these chronic diseases is often attributed to an "evolutionary mismatch," between human physiolog...
Article
Full-text available
Social status is a powerful correlate of aging-related health decline. Observational data in humans suggest that disadvantaged social status may be associated with accelerated biological aging. But establishing causality in this relationship poses challenges; experimental manipulation of human social status is not possible. In contrast, social stat...
Article
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Diet modifications are some of the most well-established aging interventions. For decades we have known that caloric restriction can dramatically increase lifespan and healthspan in organisms ranging from yeast to primates. More recently, other dietary modifications, including varying nutrient composition, have been experimentally shown to alter he...
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Objective: Our institutional Women in Medicine & Science Program (formerly the Office of Women in Medicine and Science) developed the Early Career Development Program for Women to promote the careers of women faculty. At 6 monthly sessions, participants learn relevant content (imposter syndrome, strengths, change style, career management, assertiv...
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The gut microbiota plays a fundamental role in host health and disease. Host diet is one of the most significant modulators of the gut microbial community and its metabolic activities. Evidence demonstrates that dietary patterns such as the ‘Western diet’ and perturbations in gut microbiome (dysbiosis) have strong associations with a wide range of...
Article
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Background: Western diets are associated with increased incidences of obesity, hypertension, diabetes, and hypercholesterolemia, whereas Mediterranean diets, richer in polyphenols, monounsaturated fats, fruits, vegetables, poultry, and fish, appear to have cardiometabolic health benefits. Previous work has included population-based studies with li...
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Introduction Nonhuman primates may serve as excellent models of sporadic age-associated brain β-amyloid deposition and Alzheimer’s disease pathologic changes. We examined whether a vervet nonhuman primate model recapitulated pathologic, physiologic, and behavioral features of early Alzheimer’s disease. Methods Nine middle-aged (mean = 11.2 years)...
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Background Left ventricular (LV) diastolic dysfunction often precedes heart failure with preserved ejection fraction, the dominant form of heart failure in postmenopausal women. The objective of this study was to determine the effect of oral estradiol treatment initiated early after ovariectomy on LV function and myocardial gene expression in femal...
Article
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Gut microbiome plays a fundamental role in several aspects of host health and diseases. There has been an exponential surge in the use of animal models that can mimic different phenotypes of the human intestinal ecosystem. However, data on host species-specific signatures of gut microbiome and its metabolites like short-chain fatty acids (SCFAs; i....
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Recent identification of a mammary gland-specific microbiome led to studies investigating bacteria populations in breast cancer. Malignant breast tumors have lower Lactobacillus abundance compared with benign lesions, implicating Lactobacillus as a negative regulator of breast cancer. Diet is a main determinant of gut microbial diversity. Whether d...
Article
Introduction Depressive symptoms (DS) in humans are associated with decreased resting state vagal activity, but sex seems to moderate this association. Recently, in human females DS have been associated with greater or similar cardiac vagal activity compared to men in both, clinical and non-clinical samples. A previously validated animal model of b...
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Depression is the most common mental health problem in aging persons and is a leading risk factor for physical disability, especially in women. Though antidepressant drugs such as serotonin reuptake inhibitors (SSRI) are commonly prescribed, epidemiological evidence reveals mixed effects of long-term antidepressant use on physical function and acti...
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Blood-based bioenergetic profiling provides a minimally invasive assessment of mitochondrial health shown to be related to key features of aging. Previous studies show that blood cells recapitulate mitochondrial alterations in the central nervous system under pathological conditions, including the development of Alzheimer’s disease. In this study o...
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Objective: Atherosclerosis developed during premenopausal years predicts postmenopausal atherosclerosis burden. Selective serotonin reuptake inhibitor (SSRI) antidepressants, recently approved for hot flushes, have been associated with increased ischemic stroke risk in several observational studies; however, effects on carotid artery atheroscleros...
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Cognitive impairment in older individuals is a complex trait that in population-based studies most commonly derives from an individually varying mixture of Alzheimer disease, Lewy body disease, and vascular brain injury. We investigated the molecular composition of synaptic particles from three sources: consecutive rapid autopsy brains from the adu...
Article
Selective serotonin reuptake inhibitor (SSRI) use is ubiquitous because they are widely prescribed for a number of disorders in addition to depression. Depression increases the risk of coronary heart disease (CHD). Hence, treating depression with SSRIs could reduce CHD risk. However, the effects of long term antidepressant treatment on CHD risk, as...
Article
Depression is a common and debilitating mood disorder that impacts women more often than men. The mechanisms that result in depressive behaviors are not fully understood; however, the hippocampus has been noted as a key structure in the pathophysiology of depression. In addition to neural implications of depression, the cardiovascular system is imp...
Article
Intestinal barrier dysfunction leads to microbial translocation (MT) and inflammation in vertebrate and invertebrate animal models. Age is recently recognized as a factor leading to MT, and in some human and animal model studies, MT was associated with physical function. We evaluated sarcopenia, inflammation, MT biomarkers, and muscle insulin sensi...
Chapter
Social status hierarchies are a central facet of life for numerous species. Much is known about the effects of social rank on the behavior and physiology of these species, yet the neurobiological effects have not been studied in great detail across species. In humans, low socioeconomic status is associated with poor health-related outcomes across t...
Chapter
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The scientific community has been working feverishly on the problem of obesity, particularly since the Surgeon’s General’s 2001 call to action to prevent and decrease obesity.
Article
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Current tools for automated skull stripping, normalization, and segmentation of non-human primate (NHP) brain MRI studies typically demonstrate high failure rates. Many of these failures are due to a poor initial estimate for the affine component of the transformation. The purpose of this study is to introduce a multi-atlas approach to overcome the...
Article
Selective serotonin reuptake inhibitor (SSRI) antidepressants are widely prescribed for depression and other disorders. SSRIs have become one of the most commonly used drugs in the United States, particularly by women. Acute effects on body composition and carbohydrate metabolism have been reported, but little is known regarding the effects of chro...