Factors Affecting Hematologic and Serum Biochemical Parameters in Healthy Common Marmosets (Callithrix jacchus)

Physiologic changes during development, aging, and pregnancy may affect clinical parameters. Previously available reference values have been based on samples that may include wild and captive marmosets, with little representation of geriatricor pregnant animals. Establishing reference values under various conditions would support better recognition of pathologic conditions in marmosets. One hundred and forty-seven (70 males and 77 females) healthy marmosets from a research colony were included in this study. Exclusion criteria were abnormal physical exam findings at the time of blood sampling, chronicmedications, or clinical or pathologic evidence of disease. Reference intervals were calculated for serum chemistry andhematology. Using metadata, samples were classified based on age, sex, colony source and pregnancy status. Multiple testsindicated significant differences with varying effect sizes, indicating that developing reference intervals based on metadatacan be useful. Across all the comparisons, medium or large effect sizes were observed most frequently in blood urea nitrogen (BUN), calcium, total protein, alkaline phosphatase (ALP), weight and serum albumin. We report normative clinical pathologic data for captive common marmosets through all life stages and reproductive status. Significant differences were observed in most parameters when stratifying data based on age, sex, colony source, or pregnancy, suggesting that developing reference intervals considering this information is important for clinicians.

Comparison of experimental MERS-CoV infection acquired by three individual routes of infection in the common marmoset

Two strains of Middle East Respiratory Syndrome coronavirus (MERS-CoV), England -1 and EMC/2012, were used to challenge common marmosets ( Callithrix jacchus ) by three routes of infection, aerosol, oral and intra-nasal. Animals challenged by the intra-nasal and aerosol routes presented with a mild, transient disease, while those challenged by the oral route presented with a subclinical immunological response. Animals challenged with MERS-CoV strain EMC/2012 by the aerosol route responded with primary and/or secondary pyrexia. Marmosets had minimal to mild multifocal interstitial pneumonia, with the greatest relative severity observed in animals challenged by the aerosol route. Viable virus was isolated from the host in throat swabs and lung tissue. The transient disease described is consistent with a successful host response and was characterised by upregulation of macrophage and neutrophil function observed in all animals at the time of euthanasia. Importance Middle East Respiratory Syndrome is caused by a human Coronavirus, MERS-CoV, similar to SARS-CoV-2. Humans typically exhibit with a fever, cough, shortness of breath, gastrointestinal issues and breathing difficulties which can lead to pneumonia and/or renal complications. This emerging disease resulted in the first human lethal cases in 2012 and has a case fatality rate of approximately 36%. Consequently, there is a need for medical countermeasures and appropriate animal models for their assessment. This work has demonstrated the requirement for higher concentrations of virus to cause overt disease. Challenge by the aerosol, intra-nasal and oral route resulted in no or mild disease, but all animals had an immunological response. This shows that an appropriate early immunological response is able to control the disease.

Differential Ageing of the Brain Hemispheres: Evidence from a Longitudinal Study of Hand Preferences in Common Marmosets

This paper is concerned with decreasing asymmetry of motor control in ageing. It discusses age-related changes in humans and reports a longitudinal study of hand preferences in common marmosets. An annual assessment of hand preference for holding food was recorded throughout the lifespan of 19 marmosets that lived for at least 9 years, and half of those lived for at least 11 years. Those with a left-hand preference showed a gradual reduction in the strength of their hand preference throughout adult life. No significant change in the strength of hand preference was found in right-handed marmosets. Hence, ageing has a specific effect on motor control by the right hemisphere.

Distribution of Large and Small Dorsal Root Ganglion Neurons in Common Marmosets

The aim of this study was to elucidate the size and distribution of dorsal root ganglion (DRG) neurons in non-human primates and to compare them with those of rodent DRG neurons. By measuring the size of NeuN-, NF200-, and peripherin-positive DRG neurons in the lumbar spinal cord of rats and marmosets, we found that the cell size distribution pattern was comparable in both species, although DRG neurons in marmosets were larger than those of rodents. This is the first demonstration that DRG neurons in marmosets have a bimodal size distribution, which has been well established in rodents and humans.

Spatial signatures of anesthesia-induced burst-suppression differ between primates and rodents

During deep anesthesia, the electroencephalographic (EEG) signal of the brain alternates between bursts of activity and periods of relative silence (suppressions). The origin of burst-suppression and its distribution across the brain remain matters of debate. In this work, we used functional magnetic resonance imaging (fMRI) to map the brain areas involved in anesthesia-induced burst-suppression across four mammalian species: humans, long-tailed macaques, common marmosets, and rats. At first, we determined the fMRI signatures of burst-suppression in human EEG-fMRI data. Applying this method to animal fMRI datasets, we found distinct burst-suppression signatures in all species. The burst-suppression maps revealed a marked inter-species difference: in rats the entire neocortex engaged in burst-suppression, while in primates most sensory areas were excluded—predominantly the primary visual cortex. We anticipate that the identified species-specific fMRI signatures and whole-brain maps will guide future targeted studies investigating the cellular and molecular mechanisms of burst-suppression in unconscious states.

DNA methylation age analysis of rapamycin in common marmosets

Human DNA methylation data have previously been used to develop highly accurate biomarkers of aging (“epigenetic clocks”). Subsequent studies demonstrate that similar epigenetic clocks can also be developed for mice and many other mammals. Here, we describe epigenetic clocks for common marmosets (Callithrix jacchus) based on novel DNA methylation data generated from highly conserved mammalian CpGs that were profiled using a custom Infinium array (HorvathMammalMethylChip40). From these, we developed and present here two epigenetic clocks for marmosets that are applicable to whole blood samples. We find that the human-marmoset clock for relative age exhibits moderately high age correlations in two other non-human primate species: vervet monkeys and rhesus macaques. In a separate cohort of marmosets, we tested whether intervention with rapamycin, a drug shown to extend lifespan in mice, would alter the epigenetic age of marmosets, as measured by the marmoset epigenetic clocks. These clocks did not detect significant effects of rapamycin on the epigenetic age of marmoset blood. The common marmoset stands out from other mammals in that it is not possible to build accurate estimators of sex based on DNA methylation data: the accuracy of a random forest predictor of sex (66%) was substantially lower than that observed for other mammals (which is close to 100%). Overall, the epigenetic clocks developed here for the common marmoset are expected to be useful for age estimation of wild-born animals and for anti-aging studies in this species.