Young Adult Marmosets Research Articles

Feasibility of fecal microbiota transplantation via oral gavage to safely alter gut microbiome composition in marmosets.

Disruption of microbial communities within human hosts has been associated with infection, obesity, cognitive decline, cancer risk and frailty, suggesting that microbiome-targeted therapies may be an option for improving healthspan and lifespan. The objectives of this study were to determine the feasibility of delivering fecal microbiota transplants (FMTs) to marmosets via oral gavage and to evaluate if alteration of the gut microbiome post-FMT could be achieved. This was a prospective study of marmosets housed at the Barshop Institute for Longevity and Aging Studies in San Antonio, Texas. Eligible animals included healthy young adult males (age 2-5 years) with no recent medication use. Stool from two donors was combined and administered in 0.5 ml doses to five young recipients once weekly for 3 weeks. Safety outcomes and alterations in the gut microbiome composition via 16S ribosomal RNA sequencing were compared at baseline and monthly up to 6 months post-FMT. Overall, significant differences in the percent relative abundance was seen in FMT recipients at the phylum and family levels from baseline to 1 month and baseline to 6 months post-FMT. In permutational multivariate analysis of variance analyses, treatment status (donor vs. recipient) (p = .056) and time course (p = .019) predicted β diversity (p = .056). The FMT recipients did not experience any negative health outcomes over the course of the treatment. FMT via oral gavage was safe to administer to young adult marmosets. The marmoset microbiome may be altered by FMT; however, progressive changes in the microbiome are strongly driven by the host and its baseline microbiome composition.

Age-related changes in the marmoset gut microbiome.

The gut microbiome is known to play a significant role in human health but its role in aging remains unclear. The objective of this study was to compare the gut microbiome composition between young adult and geriatric non-human primates (marmosets) as a model of human health and disease. Stool samples were collected from geriatric (8+ years) and young adult males (2-5 years). Stool 16S ribosomal RNA V4 sequences were amplified and sequenced on the Illumina MiSeq platform. Sequences were clustered into operational taxonomic units and classified via Mothur's Bayesian classifier referenced against the Greengenes database. A total of 10 young adult and 10 geriatric marmosets were included. Geriatric marmosets had a lower mean Shannon diversity compared with young marmosets (3.15 vs. 3.46; p = 0.0191). Geriatric marmosets had a significantly higher mean abundance of Proteobacteria (0.22 vs. 0.09; p = 0.0233) and lower abundance of Firmicutes (0.15 vs. 0.19; p = 0.0032) compared with young marmosets. Geriatric marmosets had a significantly higher abundance of Succinivibrionaceae (0.16 vs. 0.01; p = 0.0191) and lower abundance of Porphyromonadaceae (0.07 vs. 0.11; p = 0.0494). In summary, geriatric marmosets had significantly altered microbiome diversity and composition compared with young adult marmosets. Further studies are needed to test microbiome-targeted therapies to improve healthspan and lifespan.

Age-related changes in myelin of axons of the corpus callosum and cognitive decline in common marmosets.

Executive control is a higher-level cognitive function that involves a range of different processes that are involved in the planning, coordination, execution, and inhibition of responses. Many of the processes associated with executive control, such as response inhibition and mental flexibility, decline with age. Degeneration of white matter architecture is considered to be the one of the key factors underlying cognitive decline associated with aging. Here we investigated how white matter changes of the corpus callosum were related to cognitive aging in common marmosets (Callithrix jacchus). We hypothesized that reduction in myelin thickness, myelin density, and myelin fraction of axonal fibers in the corpus callosum would be associated with performance on a task of executive function in a small sample of geriatric marmosets (n = 4) and young adult marmosets (n = 2). Our results indicated declines in myelin thickness, density, and myelin fraction with age. Considerable variability was detected on these characteristics of myelin and cognitive performance assessed via the detoured reach task. Age-related changes in myelin in Region II of the corpus callosum were predictive of cognitive performance on the detoured reach task. Thus the detoured reach task appears to also measure aspects of corticostriatal function in addition to prefrontal cortical function.

Silencing of FUS in the common marmoset (Callithrix jacchus) brain via stereotaxic injection of an adeno-associated virus encoding shRNA

Fused in sarcoma (FUS) is an RNA binding protein that is involved in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). To establish the common marmoset (Callithrix jacchus) as a model for FTLD, we generated a stereotaxic injection-based marmoset model of FUS-silencing. We designed shRNAs against the marmoset FUS gene and generated an AAV9 virus encoding the most effective shRNA against FUS (shFUS). The AAV encoding shFUS (AAV-shFUS) was introduced into the frontal cortex of young adult marmosets, whereas AAV encoding a control shRNA was injected into the contralateral side. We obtained approximately 70–80% silencing of FUS following AAV-shFUS injection. Interestingly, FUS-silencing provoked a proliferation of astrocytes and microglias. Since FTLD is characterized by various emotional deficits, it would be helpful to establish a marmoset model of FUS-silencing in various brain tissues for investigating the pathomechanism of higher cognitive and behavioral dysfunction.

Body weight-associated differences in ovarian morphology in captive common marmoset (Callithrix jacchus)

In captivity, Callithrix jacchus (common marmoset) is on average heavier than their wild-living counterparts, and has a tendency to produce triplet litters rather than the normal twins. To provide initial basic information about possible weight-related differences among the ovaries, a morphometric study of follicular phase ovaries from 48 young adult marmosets has been carried out. Nearly 90% of these ovaries were found to contain some degree of luteal tissue composed of large and/or small cells. The luteal structures, follicles of all stages, and stroma were subjected to morphometric analysis, and these results were compared with body weight, circulating triglyceride, androstenedione, and total estrogens. Where only large luteal cells were present, the median body weight was the highest (only this group included animals over 500g) compared with mixed, or only small luteal cells, or absence of luteal cells. Furthermore, in this group plasma triglycerides were significantly higher compared to other groups, suggesting possible role of triglycerides in promoting luteinisation. Plasma androstenedione was also a critical discriminating factor, and was elevated where large luteal cells were present even as a mixture with small cells suggesting the large luteal cells to be the likely major ovarian source of this hormone and its metabolites. Additionally, the ovaries with large luteal cells compared to those containing only small or no luteal cells, had lower primordial follicle reserve associated with high levels of atresia and luteinisation among growing non-ovulatory follicles, indicating an accelerated activation, but at the same time a suboptimal environment for follicular growth.

Individual variability in visual discrimination and reversal learning performance in common marmosets

Detailed information about the characteristics of learning behavior in marmosets is useful for future marmoset research. We trained 42 marmosets in visual discrimination and reversal learning. All marmosets could learn visual discrimination, and all but one could complete reversal learning, though some marmosets failed to touch the visual stimuli and were screened out. In 87% of measurements, the final percentage of correct responses was over 95%. We quantified performance with two measures: onset trial and dynamic interval. Onset trial represents the number of trials that elapsed before the marmoset started to learn. Dynamic interval represents the number of trials from the start before reaching the final percentage of correct responses. Both measures decreased drastically as a result of the formation of discrimination learning sets. In reversal learning, both measures worsened, but the effect on onset trial was far greater. The effects of age and sex were not significant as far as we used adolescent or young adult marmosets. Unexpectedly, experimental circumstance (in the colony or isolator) had only a subtle effect on performance. However, we found that marmosets from different families exhibited different learning process characteristics, suggesting some family effect on learning.

In Vitro Synthesis and Characterization of a Cartilaginous Meniscus Grown from Isolated Temporomandibular Chondroprogenitor Cells

Internal derangement of the temporomandibular joint can lead to perforation of the intra-articular meniscus and osteoarthritic degeneration. Current methods of repairing damaged menisci are limited by lack of biological compatibility of graft materials. This project aimed to synthesise and characterise a primate cartilaginous meniscus in vitro from harvested mandibular chondroprogenitor cells. Isolated cells from the mandibular cartilage of 12 young adult marmosets, aged 9-12 months, were grown in monolayer culture. After 21 days confluent colonies were resuspended and dispersed into a unpolymerised solution of type I collagen and fibrinogen. The resultant cell suspension was infiltrated into a resorbable type I collagen sponge carrier and allowed to polymerise. Aliquots of the cell-infiltrated sponge were maintained in organ culture for a further 14 days. Cultures were characterised using histochemical and immunocytochemical localisation of collagen and proteoglycan species. Two-thirds of cells in confluent 21-day monolayers expressed cartilage-specific type II collagen and chondroitin-4-sulphate. After 35 days organ cultures had formed a viable, organised, three-dimensional tissue mass consisting of mature chondrocytic cells interspersed in a dense cartilaginous matrix. The cartilaginous tissue generated in vitro may have potential application in the repair or replacement of damaged menisci in vivo.

The evolution and distribution of morphological changes in the nervous system of the common marmoset following the acute administration of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine

Six young adult marmosets received 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in multiple doses (total 8-16 mg/kg over 2-13 days) sufficient to produce a parkinsonian syndrome and were killed up to 3.5 months later. Cellular changes were found in the substantia nigra, ventral tegmental area, and hypothalamus. The earliest histological abnormalities were axonal swellings in proximal parts of nigrostriatal axons. Subsequent changes in the substantia nigra were reduced Nissl staining, reduced cell volume, and aggregation and loss of melanin granules. Other effects were reduced nuclear and nucleolar volumes, depletion of cells, and hyperplasia of glial cells. Shrunken cytoplasm and nuclei stained uniformly with eosin, and no cells showed cytoplasmic swellings or inclusions. These cellular alterations, with nuclear changes resembling karyolysis, do not occur in Parkinson's disease, which is characterised by Lewy body inclusions and signs of chromatolysis. The rapid appearance of axonal swellings, disruption of Nissl substance, and cell shrinkage suggest an insult to energy producing mechanisms. In this study, the absence of histological evidence of toxicity in the locus coeruleus and also in the substantia innominata and in serotonergic cell groups is unlike the more widespread degenerative changes of Parkinson's disease.

Collagen fibre bundles of the normal marginal gingiva in the marmoset

The architecture of the gingival and interdental ligaments was studied in celloidin-embedded sections of tissue from young adult marmosets. The animals were free of clinical or histologic manifestations of inflammatory gingival disease. The fibre groups classically described were observed. In addition, several groups of fibres which do not fit into the previous classification were present. The semicircular fibres arise from the cementum near the cementum enamel junction, traverse the free marginal, facial and lingual gingiva, and insert into a comparable position on the opposite side of the tooth at a level just apical to the circular fibres. The transgingival fibres arise from the cementum of one tooth and traverse the free marginal gingiva of an adjacent tooth, and the intergingival fibres course in the free marginal gingiva on both the facial and lingual surfaces of the teeth. Since these fibre groups make up the bulk of the connective tissue framework of the marginal gingival tissues, and they arise from the root surfaces or gingiva of adjacent teeth, there is a major interdependence among the various segments of the gingiva.

Entamoeba gingivalis in periodontal disease.

STUDIES ON THE BIOLOGY OF THE PERIODONTIUM OF MARMOSETS: IX. EFFECT OF PARATHYROID HORMONE ON THE ALVEOLAR BONE OF MARMOSETS PRETREATED WITH FLUORIDATED AND NONFLUORIDATED DRINKING WATER Levy, B. M . , Dreizen, S.,Bernick, S., and Hampton, J. K., Jr. J. Dent. Res., 49:816, 1970 Forty-four young adult marmosets were divided into two groups of 20 and 24 animals each. The two groups were fed normal diets with the latter receiving drinking water containing 50 ppm fluoride. After five months twelve and ten animals from the above groups respectively were given parathyroid hormone in divided doses. The remaining marmosets served as controls and all animals were sacrificed following administration of the parathyroid hormone. The skulls were fixed and studied histologically. The results showed that pretreatment of animals with fluoridated drinking water gave minimal histologic evidence of alveolar bone resorption when injected with 300 to 600 U S P units of parathyroid hormone. Fluoride pretreated animals injected with 800 U S P units of parathyroid hormone showed a partial suppression of alveolar bone loss over the control group. University of Texas Dental Science Institute at Houston, Houston, Texas 77025. QUANTITATIVE PARAMETERS OF EARLY HUMAN GINGIVAL INFLAMMATION Schroeder, H. E . Arch. Oral Biol. 15:383, 1970 Ten biopsies were taken from human gingiva six to 24 months after eruption of premolar teeth indicated for extraction for orthodontic purposes. All teeth had a PMA of zero or one. Microscopic examination of prepared specimens revealed no evidence morphologically of reduced ameloblasts present after one year. The volume of leukocytes was greater cervically than apically with the maximum at the bottom of the sulcus. The thickness of the attached epithelium was also greater coronally than apically. Polymorphonuclear leukocytes were the prevailing cells in the epithelium and they transmigrated the epithelial attachment. Plasma cells were the prevailing cells in the connective tissue. The distribution of leukocytes was not correlated with the area or thickness of the epithelial attachment. The degree of inflammation observed clinically appeared to be the result of only one measurement, that is, the extension of inflammation into the connective tissue. Laboratory of Electron Microscopy, Department of Operative Dentistry and Periodontology, Dental Institute, University of Zurich, Zurich, Switzerland.