Biology subjects

Bliss-Moreau, E.

Publications and source records attributed to Bliss-Moreau, E..

11 recordsLinked to original sources

bioRxiv2026

Loss of calbindin and rise in pT217-tau in aging monkey prefrontal cortical dendrites

INTRODUCTION: Tau pathology in Alzheimers disease preferentially afflicts excitatory neurons in the limbic and association cortices that utilize high levels of calcium signaling to perform cognitive operations. This includes the layer III pyramidal cells in the dorsolateral prefrontal cortex (dlPFC) that subserve higher cognition, which express the calcium-binding protein, calbindin, when young and healthy, but lose calbindin and develop tangles and degenerate in Alzheimers disease (AD). These data suggest that loss of calbindin may be associated with the emergence of tau pathology. However, the relationship between calbindin and early-stage, soluble tau pathology is challenging to study in human brains, as soluble pTau dephosphorylates within 15min postmortem. In contrast, the relationship between calbindin and soluble pT217-tau expression can be studied in aging macaques with naturally-occurring tau pathology, where perfusion fixation is possible to capture phosphorylation state in situ. METHODS: The current study used multiple-label-immunofluorescence to label MAP2-positive dlPFC layer III pyramidal cells for calbindin and pT217-tau in macaque brains across the adult age span (8-34.5yrs). The study employed a semi-automated CellProfiler workflow to identify labeled pyramidal cell dendrites the cellular compartment where tau pathology begins in AD. RESULTS: Calbindin expression decreased with age, while pT217Tau increased with age. Specifically, the ratio of calbindin/pT217-tau within a dendrite decreased with age, and was especially prominent in the aged macaques with long-term inflammatory disorders. DISCUSSION: These data suggest that the loss of calbindin in dendrites with advancing age, and especially with inflammation, contributes to the rise of tau pathology and the risk of AD.

neuroscience↗

bioRxiv2025

Cellular basis for cortical network aging in primates

Large-scale brain networks are vulnerable to change with aging and become dysregulated. How these networks are altered at the cellular level remains unclear owing to challenges of bridging data across scales. Here, we integrate in vivo cortical similarity networks with whole brain spatial transcriptomics to characterize the aging brain in a lifespan cohort of macaques (N=64, ages 1-26 years). Deep-layer excitatory neurons and oligodendrocytes emerged as dominant correlates of cortical similarity, linking infragranular cell type composition to macroscopic network structure. Age-related declines in network strength were most pronounced in transmodal networks, including default mode and limbic, and aligned with regions enriched in inhibitory and glial cell types. Parvalbumin-enriched chandelier cells showed the strongest association with regional vulnerability, suggesting a role in network disconnection. Cell-type enrichment was conserved across species, with both human and macaque transcriptomic data aligning with the cortical functional hierarchy. These findings uncover a cellular basis for cortical network aging and highlight the value of imaging-transcriptomic integration across scales.

neuroscience↗

bioRxiv2023

Intragroup sociality drives individual participation in intergroup competition in an urban-dwelling nonhuman primate

There is significant variability in the extent to which individuals from group-living species participate in intergroup competition (IGC) over resources. Such variability may be particularly robust in human-impacted environments, wherein anthropogenic resources may strongly impact intergroup overlap and competition. Examining the socio-ecological causal factors driving these differences can shed new lights on animals costs-benefits trade-offs driving engagement in such interactions. Here we use (peri)urban-dwelling rhesus macaques (Macaca mulatta) as model-systems to examine how individual differences in socio-ecological characteristics (i.e., animals sex, rank, and affiliative connections) may influence propensities to participate in IGC in anthropogenic environments. We found that participation was strongly influenced by individuals affiliative connections. Interestingly, monkeys with more coalitionary support partners had higher IGC participation, but this was more pronounced for individuals that are more peripheral in their proximity and multilayer affiliative networks, compared to more socially central individuals. Moreover, males and low-ranking individuals were more likely to participate in IGC. Our findings suggest that differential access to socio-ecological resources likely drives IGC participation. The evaluation of such inter-individual differences in socio-ecological flexibility and decision-making in dynamic environments is critical for future research related to the links between behavioural ecology, health outcomes, and human-wildlife co-existence in anthropogenic landscapes.

animal behavior and cognition↗

bioRxiv2021

OpenMonkeyChallenge: Dataset and Benchmark Challenges for Pose Tracking of Non-human Primates

The ability to automatically track non-human primates as they move through the world is important for several subfields in biology and biomedicine. Inspired by the recent success of computer vision models enabled by benchmark challenges (e.g., object detection), we propose a new benchmark challenge called OpenMonkeyChallenge that facilitates collective community efforts through an annual competition to build generalizable non- human primate pose tracking models. To host the benchmark challenge, we provide a new public dataset consisting of 111,529 annotated (17 body landmarks) photographs of non-human primates in naturalistic contexts obtained from various sources including the internet, three National Primate Research Centers, and the Minnesota Zoo. Such annotated datasets will be used for the training and testing datasets to develop generalizable models with standardized evaluation metrics. We demonstrate the effectiveness of our dataset quantitatively by comparing it with existing datasets based on seven state-of-the-art pose tracking models.

animal behavior and cognition↗

bioRxiv2021

A comparative network approach to assess the social-ecological underpinnings of zoonotic outbreaks at human-wildlife interfaces

O_LIPandemics caused by wildlife-origin pathogens, like COVID-19, highlight the importance of understanding the ecology of zoonotic transmission and outbreaks among wildlife populations at human-wildlife interfaces. To-date, the relative effects of human-wildlife and wildlife-wildlife interactions on the likelihood of such outbreaks remain unclear. C_LIO_LIIn this study, we used social network analysis and epidemiological Susceptible Infected Recovered (SIR) models, to track zoonotic outbreaks through wild animals joint propensities to engage in social-ecological co-interactions with humans, and their social grooming interactions with conspecifics. C_LIO_LIWe collected behavioral and demographic data on 10 groups of macaques (Macaca spp.) living in (peri)urban environments across Asia. Outbreak sizes predicted by the SIR models were related to structural features of the social networks, and particular properties of individual animals connectivity within those networks. C_LIO_LIOutbreak sizes were larger when the first-infected animal was highly central, in both types of networks. Across host-species, particularly for rhesus and bonnet macaques, the effects of network centrality on outbreak sizes were stronger through macaques human co-interaction networks compared to grooming networks. C_LIO_LIOur findings, independent of pathogen-transmissibility, suggest that wildlife populations in the Anthropocene are vulnerable to zoonosis more so due to their propensities to aggregate around anthropogenic factors than their gregariousness with conspecifics. Thus, the costs of zoonotic outbreaks may outweigh the potential/perceived benefits of jointly interacting with humans to procure anthropogenic food. From One Health perspectives, animals that consistently interact with both humans and conspecifics across time and space are useful targets for disease spillover assessments and control. C_LI

ecology↗

bioRxiv2021

Social Housing Status Impacts Rhesus Monkeys' Affective Responding in Classic Threat Processing Tasks

The established literature clearly demonstrates that whether or not monkeys are socially reared has long term consequences for their affective behavior. Yet, in the context of behavioral neuroscience and pharmacological studies, social context of adult animals is often ignored. When social context has been studied in adult monkeys, such studies have typically focused on welfare-related issues, as social isolation often leads to the development of abnormal behavior, rather than the impact on outcomes in behavioral neuroscience studies. Variation in social housing conditions for adult animals could have an impact on affective responding and may have significant implications for the interpretation of data from biopsychiatry and behavioral neuroscience studies. We evaluated the affective reactivity of rhesus monkeys (Macaca mulatta) maintained in one of four housing conditions (individually-housed, grate-paired, intermittently-paired, and continuously-paired) using two classic threat processing tasks--a test of responsivity to objects and the Human Intruder Test. Individually-housed monkeys exhibited consistently blunted sensitivity to ostensibly threatening stimuli as compared to socially-housed monkeys. Within the three socially-housed conditions, intermittently- and continuously-paired monkeys behaved similarly to each other and grate-paired monkeys exhibited relatively enhanced sensitivity to threatening stimuli. These findings suggest that the adult housing conditions of monkeys can robustly modulate affective responding in a way that may be consistent with behavioral phenotypes observed in human psychiatric conditions. Results are considered in the context of the broad behavioral and psychiatric neuroscience literatures, which have historically used individually-housed animals, pointing to the potential need to reconsider inferences drawn from those studies.

animal behavior and cognition↗

bioRxiv2020

A pragmatic reevaluation of the efficacy of nonhuman primate optogenetics

Translational neuroscience is committed to generating discoveries in the laboratory that ultimately can improve human lives. Optogenetics has received considerable attention because of its demonstrated promise in rodent brains to manipulate cells and circuits. In a recent report, Tremblay and colleagues (2020) introduce an open resource detailing optogenetic studies of the nonhuman primate (NHP) brain and make robust claims about the translatability of the technology. We propose that their quantitative (e.g., a 91% success rate) and theoretical claims are questionable because the data were analyzed at a level relevant to the rodent but not NHP brain, injections were clustered within a few monkeys in a few studies in a few brain regions, and their definitions of success was not clearly relevant to human neuropsychiatric disease. A reanalysis of the data with a modified definition of success that included a behavioral and biological effect revealed an 62.5% success rate that was lower when considering only strong outcomes (53.1%). This calls into question the current efficacy of optogenetic techniques in the NHP brain and suggests that we are a long way from being able to leverage them in "the service of patients with neurological or psychiatric conditions" as the Tremblay report claims.

neuroscience↗

bioRxiv2020

Neuroanatomical abnormalities in a nonhuman primate model of congenital Zika virus infection

Zika virus (ZIKV) infection of pregnant women can cause major congenital neuronal abnormalities. In the present study, we evaluated neuropathological consequences of fetal ZIKV exposure in rhesus macaques, a highly translatable animal model for human neural development. Quantitative neuroanatomical analyses of the nearly full-term brains of fetuses infected with ZIKV at gestational days 50, 64, and 90, and three procedure-matched sham-inoculated controls were carried out. Whole tissue sections across a complete cerebral hemisphere were evaluated using immunohistochemical and neuroanatomical staining techniques to detect virus localization, identify affected cell types and evaluate gross neuroanatomical abnormalities. None of the subjects were microcephalic. Immunohistochemical staining revealed the presence of ZIKV in the frontal lobe, which contained activated microglia and showed increased apoptosis of immature neurons. ZIKV-infected animals exhibited macrostructural changes within the occipital lobe, including a reduction in gyrification as well as a higher proportion of white matter. Finally, the ZIKV-infected subjects had abnormalities throughout the visual pathway, including disorganization within the lateral geniculate nucleus (LGN) and primary visual cortex (V1). Regional differences tracked with the temporal patterns of the developing brain and likely reflect the neural progenitor cell tropism ZIKV exhibits - painting a picture of inflammatory processes related to viral infiltration sweeping through the cortex, followed by a wave of cell death resulting in morphological changes. These findings may help explain why some infants born with normal sized heads during the ZIKV epidemic manifest developmental challenges as they age, and ultimately may contribute to developing effective treatments and interventions. One sentence summaryMacaque fetuses infected with Zika virus show both macro- and micro-scale neuropathological abnormalities, including decreased gyrencephality, relative increases in cortical white matter, activation of glia, and increased apoptosis.

neuroscience↗

bioRxiv2018

Quantitative analysis of synaptic pathology and neuroinflammation: an initial study in a female rhesus monkey model of the “synaptic” phase of Alzheimer’s disease

BackgroundSoluble oligomers of the A{beta} peptide (A{beta}Os) are toxins that target and disrupt synapses. Generation of A{beta}Os has been recently recognized as a probable initiating event in Alzheimers disease (AD), leading to cognitive impairment. There is a translational gap in AD studies, with promising drugs developed based on work in rodent models failing in AD patients in clinical trials. Additionally, although women have a two-fold greater lifetime risk of developing AD compared to men, females have not been a focus of preclinical studies. Thus, we sought to develop a model of A{beta}O toxicity in female rhesus monkeys, to take advantage of the more highly differentiated cortical structure in this species as well as the similarities in the endocrine system between rhesus monkeys and humans.\n\nMethodsRepeated intracerebroventricular (i.c.v) injections of A{beta}Os were performed in adult female rhesus monkeys. Controls were unoperated aged matched monkeys. High-resolution confocal microscopy and morphometric analysis of Alexa 568 (A568) filled neurons were used to evaluate synaptic, neuronal, and glial markers in the dorsolateral prefrontal cortex (dlPFC) and hippocampus after A{beta}O injections. Cerebrospinal fluid (CSF) and brain tissue were also collected and analyzed for biomarkers of AD pathology, including: phosphorylated Tau protein (pTau), total Tau, A{beta}1-42, A{beta}1-40 and TNF- levels.\n\nResultsHere, we report that A{beta}O injection into the lateral ventricle of the brain induces loss of 37% of thin spines in targeted dlPFC neurons, an area highly vulnerable in AD and aging. Further, A{beta}Os associate with the synaptic marker PSD95, inducing loss of more than 60% of local excitatory synapses. A{beta}Os induce a robust neuroinflammatory response in the hippocampus, far from the injection site, with numerous activated ameboid microglia and TNF- release. Finally, A{beta}Os increased CSF levels of A{beta}1-42, pTau Ser396 and pTau Ser199, but not A{beta}1-40 or total Tau.\n\nConclusionsThese initial findings from detailed quantitative analysis of effects of A{beta}O administration on synapses in a female nonhuman primate model are a very promising step toward understanding the mechanism of early AD pathogenesis in the primate brain, and may help develop an effective disease-modifying therapy of high relevance to womens health.

neuroscience↗

bioRxiv2018

Timing of Cyclic Estradiol Treatment Differentially Affects Cognition in Aged Female Rhesus Monkeys

Some evidence suggests that there may be a limited \"window of opportunity\" for beneficial effects of hormone therapy on physiology after menopause in women. We tested, in aged, surgically menopausal (ovariectomized) rhesus monkeys, whether the timing of cyclic estradiol (E2) treatment impacted its effect on cognitive function. Monkeys were assigned to one of four treatment conditions after ovariectomy: either vehicle or E2 treatment for the duration of the protocol, vehicle for the first 2 years of the protocol followed by E2 for the remainder (delayed treatment), or E2 for the first year of the protocol followed by vehicle for the remainder (withdrawn treatment). Delayed treatment addressed the hypothesis that E2 treatment initiated more than 2 years after ovariectomy would have a reduced effect on cognitive function. Withdrawn treatment mirrors current clinical advice to women to use hormone therapy in the initial post-menopausal period then discontinue it. Two periods of cognitive testing assessed treatment effects on cognition over time. E2 treatment predominantly affected a prefrontal cortex-dependent test of spatiotemporal working memory (delayed response). Monkeys with delayed E2 treatment improved in delayed response performance over time, whereas vehicle-treated monkeys declined. Monkeys with withdrawn E2 treatment maintained their performance across assessments, as did monkeys treated with E2 across the entire protocol. These findings suggest that a \"window of opportunity\" for hormone treatment after cessation of ovarian function, if present in nonhuman primates, lasts longer than 2 years. It also supports the notion that beneficial effects of hormone therapy may persist after discontinuation of treatment.

neuroscience↗

bioRxiv2018

Estradiol treatment in a nonhuman primate model of menopause preserves affective reactivity

As humans age, their affective lives tend to become more positive and less negative. This phenomenon, known as the positivity effect (or positivity bias), occurs even as aging leads to declines in health and cognitive outcomes. Despite these well documented effects in humans, extent to which affective processes change in nonhuman animals, and in particular nonhuman primates - is unclear. As a first step towards developing a model for human affective aging in rhesus monkeys (Macaca mulatta), we tested aged, surgically menopausal aged and middle-aged gonadally intact female rhesus monkeys on a classic index of affective reactivity in monkeys, the Human Intruder task. The Human Intruder task evaluates behavioral responses to varying levels of threat. Aged, surgically menopausal monkeys received hormone replacement therapy consisting of a cyclic estradiol regimen, or vehicle injections as a control. Average responsivity to threat did not vary by condition, but middle aged monkeys and aged monkeys on estradiol were more reactive to the most potent level of threat than to a moderate level of threat, replicating previously published results in other age groups and male monkeys. In contrast, aged monkeys not on estradiol did not show such calibration to threat level. These findings suggest that estrogen may be important for maintaining more youthful affective responding. They also illustrate the utility of behavioral assays of affective reactivity in nonhuman primate models of cognitive and reproductive aging in humans.

animal behavior and cognition↗