scholarly journals REVERSE TRANSLATION OF HUMAN BIO-AGING MEASURES TO CYNOMOLGUS MONKEYS TO TEST ASSOCIATIONS WITH DOMINANCE RANK

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S349-S349
Author(s):  
Noah Snyder-Mackler ◽  
Carol Shively ◽  
Tom Register ◽  
Daniel W Belsky
Keyword(s):  
Social Status ◽  
Dominance Rank ◽  
Blood Chemistry ◽  
Experimental Manipulation ◽  
Biological Aging ◽  
Primate Model ◽  
Cynomolgus Monkeys ◽  
Health Decline ◽  
Using Data ◽  
Human Primate

Abstract 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 status can be experimentally manipulated non-human primates (e.g. Snyder-Mackler 2016 Science). We conducted analysis to reverse-translate blood-chemistry of biological aging to cynomolgus monkeys using data from several hundred animals in the Wake Primate Center breeding colony. We are applying these measures in an independent sample of monkeys with ascertained dominance rank to test replication in the non-human primate model of the human social gradient in biological aging. Parallel analysis of DNA methylation-based measures of biological aging are ongoing and should be available to present by Fall 2019. Results will inform potential to use this non-human primate model to study social determinants of biological aging.

scholarly journals A new and spontaneous animal model for ankylosing spondylitis  is found in cynomolgus monkeys

2020 ◽  
Author(s):  
Huanhuan JIA ◽  
Meili CHEN ◽  
Xiaoling LUO ◽  
Gang HOU ◽  
Ting LUO ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Bone Formation ◽  
Disease Progression ◽  
Joint Disease ◽  
Pathological Examination ◽  
Radiographic Examination ◽  
Primate Model ◽  
Cynomolgus Monkeys ◽  
Abnormal Movements ◽  
Human Primate

Abstract Background Ankylosing spondylitis (AS) is a progressive, disabling joint disease that affects millions worldwide. There is a lack of useful disease model to conduct comprehensive mechanistic studies. Non-human primate model is a potential spontaneous model for ankylosing spondylitis (AS). Methods A group of cynomolgus monkeys with abnormal joints and abnormal movements were screened out from about 20,000 cynomolgus monkeys primarily. A 2-years follow-up study of this group of cynomolgus monkeys having joint lesions reported of spinal stiffness was performed by conducting hematological testing, radiographic examination, family aggregation analysis, pathological analysis and genetic testing. Results These diseased animals suffered from spontaneous AS with clinical features recapitulating human AS disease progression. The spontaneous incidence rate and the onset age of AS in monkeys similar to epidemiological features of AS patients. The disease progression in disease monkeys have shown bone erosion, osteophyte formation and “Bamboo-like” change. ESR, CRP IL-17, TNF-α and VEGF levels significantly increase in AS monkeys comparing with normal monkeys. Several features similar to AS patients, including cartilage destruction, cartilage ossification, chondroid metaplasia and bone formation were shown in AS monkeys pathological examination results. Both the serum bone resorption and bone formation biomarkers of AS monkeys were significantly reduce. In our current SNP sequencing results, loci that similar to AS-relative SNPs in human genome have not yet been found. Conclusions The study offers a promising non-human primate model for spontaneous ankylosing spondylitis which may serve as an excellent substitute for its pre-clinical research.

scholarly journals The establishment of a rheumatoid arthritis primate model in Macaca fascicularis

2020 ◽  
Author(s):  
Hyun Sik Na ◽  
Seon-young Lee ◽  
Hong Ki Min ◽  
Wan-je Park ◽  
Jung-hwan Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Evaluation ◽  
Autoimmune Disorder ◽  
Type Ii Collagen ◽  
Blood Chemistry ◽  
Cross Reactivity ◽  
Visual Evaluation ◽  
Primate Model ◽  
Cynomolgus Monkeys ◽  
Close Phylogenetic Relationship

Abstract Background Rheumatoid arthritis (RA) is a long-term autoimmune disorder that mostly affects the joints and leads to the destruction of cartilage. An RA model in non-human primates is especially useful because of their close phylogenetic relationship to humans in terms of cross-reactivity to compounds developed using modern drug technologies.Methods We used a collagen-induced arthritis (CIA) model in cynomolgus monkeys. CIA was induced by the immunization of chicken type II collagen. Swelling was measured as the longitudinal and transverse axes of 16 proximal interphalangeal joints.Results A new system for visual evaluation was created, with a perfect score of 16. Individual behavioral analysis was also conducted. Serum was collected once a week after the first immunization. Blood chemistry and inflammatory cytokine parameters were higher in the CIA group than in the wild type group.Conclusion In conclusion, we established CIA in cynomolgus monkeys, and the results can be used for drug evaluation models.

scholarly journals Decoupling social status and status certainty effects on health in macaques: a network approach

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2394 ◽  
Author(s):  
Jessica J. Vandeleest ◽  
Brianne A. Beisner ◽  
Darcy L. Hannibal ◽  
Amy C. Nathman ◽  
John P. Capitanio ◽  
...  
Keyword(s):  
Physical Health ◽  
Social Status ◽  
Social Life ◽  
Rhesus Macaques ◽  
Social Systems ◽  
Dominance Rank ◽  
Primate Model ◽  
Necrosis Factor Alpha ◽  
General Physical ◽  
The Impact

BackgroundAlthough a wealth of literature points to the importance of social factors on health, a detailed understanding of the complex interplay between social and biological systems is lacking. Social status is one aspect of social life that is made up of multiple structural (humans: income, education; animals: mating system, dominance rank) and relational components (perceived social status, dominance interactions). In a nonhuman primate model we use novel network techniques to decouple two components of social status, dominance rank (a commonly used measure of social status in animal models) and dominance certainty (the relative certainty vs. ambiguity of an individual’s status), allowing for a more complex examination of how social status impacts health.MethodsBehavioral observations were conducted on three outdoor captive groups of rhesus macaques (N = 252 subjects). Subjects’ general physical health (diarrhea) was assessed twice weekly, and blood was drawn once to assess biomarkers of inflammation (interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP)).ResultsDominance rank alone did not fully account for the complex way that social status exerted its effect on health. Instead, dominance certainty modified the impact of rank on biomarkers of inflammation. Specifically, high-ranked animals with more ambiguous status relationships had higher levels of inflammation than low-ranked animals, whereas little effect of rank was seen for animals with more certain status relationships. The impact of status on physical health was more straightforward: individuals with more ambiguous status relationships had more frequent diarrhea; there was marginal evidence that high-ranked animals had less frequent diarrhea.DiscussionSocial status has a complex and multi-faceted impact on individual health. Our work suggests an important role of uncertainty in one’s social status in status-health research. This work also suggests that in order to fully explore the mechanisms for how social life influences health, more complex metrics of social systems and their dynamics are needed.

scholarly journals Chronic unpredictable mild stress produces depressive-like behavior, hypercortisolemia, and metabolic dysfunction in adolescent cynomolgus monkeys

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Teng Teng ◽  
Carol A. Shively ◽  
Xuemei Li ◽  
Xiaofeng Jiang ◽  
Gretchen N. Neigh ◽  
...  
Keyword(s):  
Adolescent Depression ◽  
Mild Stress ◽  
Matched Pairs ◽  
Metabolic Dysfunction ◽  
Chronic Unpredictable Mild Stress ◽  
Hair Cortisol ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
Cynomolgus Monkeys ◽  
Human Primate

AbstractAdolescent 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 cynomolgus monkeys were divided into a chronic unpredictable mild stress (CUMS, n = 5) group and a control (CON, n = 5) group by age and weight-matched pairs. The CUMS group was exposed to multiple unpredictable mild stressors for five cycles over 55 days. At baseline, there were no differences between CUMS and CON groups. At endpoint, the CUMS group demonstrated significantly higher depressive-like behavior (huddle posture), and significantly lower locomotion compared with the CON group. Furthermore, depressive-like behavior increased from baseline to endpoint in the CUMS group, but not changed in the CON group. In the attempt for apple test, the CUMS group made significantly fewer attempts for the apple than the CON group. In the human intruder test, the CUMS group showed significantly higher anxiety-like behaviors in the stare phase than the CON group. Hair cortisol level was significantly higher in the CUMS group than the CON group at endpoint, and was also elevated from baseline to endpoint. Metabolic profiling of plasma at endpoint identified alterations in metabolite pathways which overlapped with those of adolescent depression patients. CUMS can induce depressive-like and anxiety-like behaviors, hypercortisolemia, and metabolic perturbations in adolescent cynomolgus monkeys. This is a promising model to study the mechanisms underlying adolescent depression.

Abstract 4950: Infection with Enterovirus Produces Myocarditis in a Non-Human Primate Model

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Nancy Halnon ◽  
Cheryl Cammock ◽  
Morgan Singletary ◽  
James Blanchard ◽  
Jill Skoczylas ◽  
...  
Keyword(s):  
Cardiac Tissue ◽  
Cardiac Injury ◽  
Clinical Specimen ◽  
Neutralizing Antibody ◽  
Primate Model ◽  
Cynomolgus Monkeys ◽  
Enteroviral Infection ◽  
Antibody Titers ◽  
Eosinophilic Myocarditis ◽  
Human Primate

Introduction: We performed a pilot study to establish a non-human primate model of enteroviral infection and myocarditis. Methods: Juvenile cynomolgus monkeys were inoculated via oral (n=1) or intravenous (n=8) routes with a cloned Coxsackievirus B3 (CVB-3) or a CVB-3 /Enterovirus 86 strain (CVB-MCH) isolated from a clinical specimen from a patient with fatal myocarditis. Clinical and echocardiographic assessment was performed at baseline and at days 3, 7, 14, and 28. CVB-3 neutralizing antibody titers were measured. Viral RNA was detected by RT-PCR and culture of plasma and cardiac tissue. Animals were sacrificed at 14 or 28 days and myocardium examined for viral pathology. Results: Infection was achieved by both routes with both CVB-3 strains. Viremia was detected in 6/9, resolving after day 3. All (9/9) generated neutralizing antibody. Two animals infected with 10 7 infectious units (IU) of CVB-3 became moribund and were sacrificed at day 11 and day 14. Subsequent animals received 10 6 IU of CVB-3 and appeared well until sacrificed at day 14 (n=3) or day 28 (n=1). Three infected with 10 6 IU CVB-MCH also appeared well until sacrificed at day 28. Normal ejection fraction was maintained, but four animals had minor wall motion abnormalities. Serum troponin remained normal. Virus was present in myocardium in 5/5 tested. Multiple areas of focal cardiac injury were present in all animals and included lymphocytic or eosinophilic myocarditis (n=6), focal inflammation (n= 3), myocytolysis (n=2), ischemic foci (n=4), contraction band necrosis (n=2), and hypertrophy (n=3). Active myocarditis was present in 4/5 animals at day 14 and 2/4 at day 28. Conclusions: We were able to consistently establish infection with CVB-3 in cynomolgus monkeys resulting in clinically apparent or sub clinical disease, including myocarditis or cardiac injury persisting at 28 days. Despite adequate immune responses to clear viremia, virus persisted in the myocardium. The presence of myocyte hypertrophy and injury at 28 days in this model may provide a basis for experiments aimed at modulating immune or virus induced cardiomyopathy.

scholarly journals Agonism and grooming behavior explain social status effects on physiology and gene regulation in rhesus macaques

2021 ◽  
Author(s):  
Noah D Simons ◽  
Vasiliki Michopoulos ◽  
Mark Wilson ◽  
Luis B Barreiro ◽  
Jenny Tung
Keyword(s):  
Gene Regulation ◽  
Social Status ◽  
Lived Experience ◽  
Rhesus Macaques ◽  
Dominance Rank ◽  
Experimental Studies ◽  
Experimental Manipulation ◽  
Affiliative Behavior ◽  
Behavioral Interactions ◽  
Physiological Outcomes

Variation in social status predicts molecular, physiological, and life history outcomes across a broad range of species, including our own. Experimental studies indicate that some of these relationships persist even when the physical environment is held constant. Here, we draw on data sets from one such study-experimental manipulation of dominance rank in captive female rhesus macaques-to investigate how social status shapes the lived experience of these animals to alter gene regulation, glucocorticoid physiology, and mitochondrial DNA phenotypes. We focus specifically on dominance rank-associated dimensions of the social environment, including both competitive and affiliative interactions. Our results show that simple summaries of rank-associated behavioral interactions are often better predictors of molecular and physiological outcomes than dominance rank itself. However, while measures of immune function are best explained by agonism rates, glucocorticoid-related phenotypes tend to be more closely linked to affiliative behavior. We conclude that dominance rank serves as a useful summary for investigating social environmental effects on downstream outcomes. Nevertheless, the behavioral interactions that define an individual's daily experiences reveal the proximate drivers of social status-related differences, and are especially relevant for understanding why individuals who share the same social status sometimes appear physiologically distinct.

scholarly journals Agonism and grooming behaviour explain social status effects on physiology and gene regulation in rhesus macaques

2022 ◽  
Vol 377 (1845) ◽  
Author(s):  
Noah D. Simons ◽  
Vasiliki Michopoulos ◽  
Mark Wilson ◽  
Luis B. Barreiro ◽  
Jenny Tung
Keyword(s):  
Gene Regulation ◽  
Social Status ◽  
Lived Experience ◽  
Rhesus Macaques ◽  
Dominance Rank ◽  
Experimental Studies ◽  
Experimental Manipulation ◽  
Behavioural Interactions ◽  
Physiological Outcomes ◽  
Social Environmental

Variation in social status predicts molecular, physiological and life-history outcomes across a broad range of species, including our own. Experimental studies indicate that some of these relationships persist even when the physical environment is held constant. Here, we draw on datasets from one such study—experimental manipulation of dominance rank in captive female rhesus macaques—to investigate how social status shapes the lived experience of these animals to alter gene regulation, glucocorticoid physiology and mitochondrial DNA phenotypes. We focus specifically on dominance rank-associated dimensions of the social environment, including both competitive and affiliative interactions. Our results show that simple summaries of rank-associated behavioural interactions are often better predictors of molecular and physiological outcomes than dominance rank itself. However, while measures of immune function are best explained by agonism rates, glucocorticoid-related phenotypes tend to be more closely linked to affiliative behaviour. We conclude that dominance rank serves as a useful summary for investigating social environmental effects on downstream outcomes. Nevertheless, the behavioural interactions that define an individual's daily experiences reveal the proximate drivers of social status-related differences and are especially relevant for understanding why individuals who share the same social status sometimes appear physiologically distinct. This article is part of the theme issue ‘The centennial of the pecking order: current state and future prospects for the study of dominance hierarchies’.

Hexachlorobenzene toxicity in the monkey ovary: III. Ultrastructure induced by high (10 mg/kg) dose exposure

1991 ◽  
Vol 49 ◽  
pp. 130-131
Author(s):  
A. Singh ◽  
A. Dykeman ◽  
J. Jarrelf ◽  
D. C. Villeneuve
Keyword(s):  
Present Report ◽  
Reproductive Toxicity ◽  
Control Group ◽  
Primate Model ◽  
Human Follicular Fluid ◽  
Thin Sections ◽  
Cynomolgus Monkeys ◽  
Cacodylate Buffer ◽  
Induction Cycle ◽  
Comprehensive Study

Hexachlorobenzene (HCB), a persistent and mobile organochlorine pesticide, occurs in environment. HCB has been shown to be present in human follicular fluid. An objective of the present report, which is part of a comprehensive study on reproductive toxicity of HCB, was to determine the cytologic effects of the compound on ovarian follicles in a primate model.Materials and Methods. Eight Cynomolgus monkeys were housed under controlled conditions at Animal facility of Health and Welfare, Ottawa. Animals were orally administered gelatin capsules containing HCB mixed with glucose in daily dosages of 0.0 or 10 mg/kg b.w. for 90 days; the former was the control group. On the menstrual period following completion of dosing, the monkeys underwent an induction cycle of superovulation. At necropsy, one-half of an ovary from each animal was diced into ca. 2- to 3-mm cubed specimens that were fixed by immersion in 2.5% glutaraldehyde in 0.1 M cacodylate buffer (pH 7.3). Subsequent procedures followed to obtain thin sections that were examined in a Hitachi H-7000 electron microscope have been described earlier.

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