Biology subjects

Bachevalier, J.

Publications and source records attributed to Bachevalier, J..

5 recordsLinked to original sources

bioRxiv2025

Effects of Social Status on Reproductive Success, Physiology and Maternal Care in Socially housed Female Rhesus Macaques

This study examined the long-term effects of low social status on reproductive success and seasonal changes in reproductive and stress hormones of adult female rhesus macaques. Rhesus are a matriarchal, matrilineal species that form hierarchical social hierarchies maintained by aggression. Thus, animals in the bottom of the hierarchy (low social status: subordinate) experience high levels of aggression from those in higher social ranks and therefore must remain vigilant. Social subordination generates chronic psychosocial stress and could negatively impact reproductive function. Twenty-seven adult female rhesus monkeys (13 dominant -DOM-, 14 subordinate -SUB-; 8-11 years old) were studied for stress neuroendocrine function -measuring basal plasma levels of cortisol-, as well as for reproductive endocrine function -measuring basal levels of estradiol (E2). In addition, we examined the reproductive success rates of these females (defined as number of live births/years with male access), their success rates raising infants that survived to 1 year, and the characteristics and effectiveness of their maternal care. Our findings show significantly lower reproductive success rates in SUB than DOM females, blunted E2 seasonal changes, driven by higher E2 levels in the anovulatory season and more attentive maternal care of offspring early in life than dominant females. Age at first birth was negatively associated with infant survival rate across ranks. Interestingly, higher levels of reproductive hormones (E2) during the anovulatory season predicted lower reproductive success, although the effect was driven by animals lactating at that point. Overall, these findings suggest that subordinate female macaques show a phenotype consistent with impaired reproductive function. Simple SummaryThis study examined the long-term effects of low social status on reproductive success and seasonality of reproductive and stress physiology of female rhesus monkeys. The despotic rhesus social hierarchy is matrilineal and maintained by aggression. Males leave their natal group in bachelor groups around puberty, but females remain, so social status of group members is passed down the female line. Rhesus with low social status (subordinate) experience significantly more aggression and harassment than their higher-ranking counter parts (dominant). This makes rhesus macaques an ideal model for studying chronic psychosocial stress and its long-term effects. Our findings show significantly lower reproductive success rates (number of live births based on access to males; lower infant survival rates) in subordinate than dominant females. Subordinate females also show blunted seasonal changes of the gonadal hormone estradiol (E2), driven by higher E2 levels in the anovulatory season than dominant animals, as well as more attentive maternal care of offspring early in life than dominant animals. Age at first birth was negatively associated with infant survival rate across ranks. Interestingly, higher levels of reproductive hormones (E2) during the anovulatory season were associated with lower reproductive success, although the effect was driven by animals lactating at that point. Overall, these findings suggest that female macaques with lower social status show a phenotype consistent with impaired reproductive function, though the biological mechanisms involved need to be further explored.

developmental biology↗

bioRxiv2025

The effects of chronic social stress on cognitive flexibility in adult female macaques

Chronic social subordination stress in macaques, particularly beginning early in life, is associated with negative health and cognitive aging outcomes. Utilizing a longitudinal, translational monkey model of early life stress in Rhesus macaques (Macaca mulatta), we assessed adult female cognitive performance that had received social subordination stress associated with Low Social Status (LSS) since birth. This chronic social stress in lower ranked monkeys produces physiological stress responses that over time can accelerate biological and cognitive aging. We compared 14 adult females of Low Birth Rank that had received higher levels of social subordination stress since infancy with 11 adult females of High Birth Rank that had received lower levels of chronic social stress. We followed these two groups longitudinally from birth to adolescence to assess long-term behavioral, physiological, and neural consequences of social stress. As they reached adulthood (ages 7-8 years), we measured executive function/cognitive flexibility using the Intra-/Extra-dimensional shift task (ID/ED), relevant for age-related cognitive decline. Only mild differences between High and Low ranking subjects were observed on the simple discrimination, and the reversal learning stages of the task. We did find an interaction between High Birth Rank and performance across the three dimensional-shift stages that was not present in the low-ranking subjects. Thus, although at this first age, we did not yet detect the presence of accelerated cognitive decline following chronic social stress, the low-ranking females showed mild deficits in cognitive flexibility compared to high-ranking subjects. We discuss additional factors impacting performance, and comparisons with neuroimaging data.

neuroscience↗

bioRxiv2025

Structural Effects of Low Social Status and Obesogenic Diet on Social and Emotional Neurocircuits in Female Macaques: A Longitudinal Study from Infancy to Adulthood

A substantial body of literature has demonstrated a consistent link between psychosocial stress and obesity in children, particularly in those from low socioeconomic backgrounds. Despite evidence indicating a complex interplay between stress, diet and obesity, there is a limited understanding of the specific versus potentially synergistic effects of obesity and stress on brain structural and functional development. This study investigates the developmental and long-term brain structural alterations resulting from exposure to chronic social stress due to low (subordinate -SUB-) social status and postnatal obesogenic diets. Forty-one female rhesus macaques (Dominants -DOM-, n=21; Subordinates -SUB-, n=20) were assigned to either only low-calorie diet (LCD) or to both high-calorie diet (HCD) and LCD (Choice diet) from birth through the juvenile period. After menarche, all subjects were maintained on a LCD-only diet through adulthood. Twenty-seven animals (DOM: n=13, SUB: n=14) were studied again in adulthood to investigate the long-term effects of early diet and social rank on brain structure. Cumulative Kcal consumption was measured from birth through 16 months and body weights were measured at all time points. Overall, the findings show specific effects of obesogenic diet and psychosocial stress on cortical and corticolimbic brain regions. Animals with access to the obesogenic diet had larger overall brain size (measured as intracranial volume -ICV-) and larger overall volumes of prefrontal cortex, insula, superior temporal sulcus (defined as temporo-parieto-occipital area rostral and caudal regions (TPOr and TPOc)) than those in the low-calorie diet. Most of these regional diet effects, except for the insula, were driven by general effects of the diet on brain size. The diet effects were lost when adding the adult data to the longitudinal analysis, suggesting transient effects of obesogenic diets while the animals were consuming it, but not long-term, persistent effects. These findings highlight the potential of brain rescue mechanisms that could offset lasting developmental effects of early-life obesogenic diet consumption. With respect to social rank, SUB exhibited larger volumes in brain regions related to social cognition and emotional processing than DOM animals. When the adult data was added to the longitudinal analysis, the effects of social rank were prominent in the hippocampus, superior temporal sulcus, temporo-parieto-occipital rostral region, and the temporal auditory cortices after ICV data correction, suggesting long-term, persistent and cumulative effects of these social experiences, in contrast to the transient diet effects.

neuroscience↗

bioRxiv2020

Validation of the Social Responsiveness Scale (SRS) to screen for atypical social behaviors in juvenile macaques

Primates form strong social bonds and depend on social relationships and networks that provide shared resources and protection critical for survival. Social deficits such as those present in autism spectrum disorder (ASD) and other psychiatric disorders hinder the individual’s functioning in communities. Given that early diagnosis and intervention can improve outcomes and trajectories of ASD, there is a great need for tools to identify early markers for screening/diagnosis, and for translational animal models to uncover biological mechanisms and develop treatments. One of the most widely used screening tools for ASD in children is the Social Responsiveness Scale (SRS), a quantitative measure used to identify individuals with atypical social behaviors. The SRS has been adapted for use in adult rhesus monkeys (Macaca mulatta) –a species very close to humans in terms of social behavior, brain anatomy/connectivity and development– but has not yet been validated or adapted for a necessary downward extension to younger ages matching those for ASD diagnosis in children. The goal of the present study was to adapt and validate the adult macaque SRS (mSRS) in juvenile macaques with age equivalent to 4-6 yr old human children. Expert primate coders modified the mSRS to adapt it to rate atypical social behaviors in juvenile macaques living in complex social groups at the Yerkes National Primate Research Center. Construct and face validity of this juvenile mSRS (jmSRS) was determined based on well-established and operationalized measures of social and non-social behaviors in this species using traditional behavioral observations. We found that the jmSRS identifies variability in social responsiveness of juvenile rhesus monkeys and shows strong construct/predictive validity, as well as sensitivity to detect atypical social behaviors in young male and female macaques across social status. Thus, the jmSRS provides a promising tool for translational research on macaque models of children social disorders.View Full Text

animal behavior and cognition↗

bioRxiv2020

Sexually dimorphic responses to MPTP found in microglia, inflammation and gut microbiota in a progressive monkey model of Parkinson's disease

Inflammation has been linked to the development of nonmotor symptoms in Parkinsons disease (PD), which greatly impact patients quality of life and can often precede motor symptoms. Suitable animal models are critical for our understanding of the mechanisms underlying disease and the associated prodromal disturbances. The neurotoxin 1- methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkey model is commonly seen as a "gold standard" model that closely mimics the clinical motor symptoms and the nigrostriatal dopaminergic loss of PD, however MPTP toxicity extends to other nondopaminergic regions. Yet, there are limited reports monitoring the MPTP-induced progressive central and peripheral inflammation as well as other nonmotor symptoms such as gastrointestinal function and microbiota. The main objective of this study is to gain a broader understanding of central and peripheral inflammatory dysfunction triggered by exposure to a neurotoxicant known to degenerate nigral dopaminergic neurons in order to understand the potential role of inflammation in prodromal/pre-motor features of PD-like degeneration in a progressive non-human primate model of the disease. We measured inflammatory proteins in plasma and CSF and performed [18F]FEPPA PET scans to evaluate translocator proteins (TSPO) or microglial activation in a small cohort of rhesus monkeys (n=5) given weekly low doses of MPTP (0.2-0.8 mg/kg, im). Additionally, monkeys were evaluated for working memory and executive function using various behavior tasks and for gastrointestinal hyperpermeability and microbiota composition. Monkeys were also treated with novel TNF inhibitor XPro1595 (10mg/kg, n=3) or vehicle (n=2) every three days starting 11 weeks after the initiation of MPTP to determine whether nonmotor symptoms are tied to TNF signaling and whether XPro1595 would alter inflammation and microglial behavior in a progressive model of PD. Our analyses revealed sex-dependent sensitivity to MPTP that resulted in early microglial activation by PET, acute plasma IL-6 and CSF TNF, and earlier parkinsonism as measured by motor deficits in males compared to female monkeys. Sex differences were also identified in microbiota and their metabolites and targeted short chain fatty acids at both basal levels and in response to MPTP. Both sexes displayed cognitive impairment prior to a significant motor phenotype. Importantly, XPro1595 shifted peripheral and central inflammation, and significantly reduced CD68-immunoreactivity in the colon. As such, our findings revealed a sexually dimorphic inflammatory response to chronic MPTP treatment and suggest that males may have higher vulnerability than females to inflammation-induced degeneration. If these findings reflect potential differences in humans, these sex differences have significant implications for therapeutic development of inflammatory targets in the clinic.

neuroscience↗