Adult Vervet Monkeys Research Articles

First Biodistribution Study of [68Ga]Ga-NOTA-Insulin Following Intranasal Administration in Adult Vervet Monkeys.

Intranasal insulin (INI) is being explored as a treatment for Alzheimer's disease (AD). Improved memory, functional ability, and cerebrospinal fluid (CSF) AD biomarker profiles have been observed following INI administration. However, the method of intranasal delivery may significantly affect outcomes. To show reliable delivery of insulin to the brain using the Aptar Cartridge Pump System (CPS) intranasal delivery system. To visualize INI biodistribution, we developed a novel PET radiotracer, Gallium 68-radiolabeled (NOTA-conjugated) insulin, [68Ga]Ga-NOTA-insulin. We used the Aptar CPS to administer [68Ga]Ga-NOTA-insulin to anesthetized healthy adult vervet monkeys and measured brain regional activity and whole-body dosimetry following PET/CT scans. We observed brain penetration of [68Ga]Ga-NOTA-insulin following intranasal administration with the Aptar CPS. Radioactive uptake was seen in multiple regions, including the amygdala, putamen, hypothalamus, hippocampus, and choroid plexus. A safety profile and whole-body dosimetry were also established in a second cohort of vervets. Safety was confirmed: vitals remained stable, blood glucose levels were unchanged, and no organ was exposed to more than 2.5 mSv of radioactivity. Extrapolations from vervet organ distribution allowed for estimation of the [68Ga]Ga-NOTA-insulin absorbed dose in humans, and the maximum dose of [68Ga]Ga-NOTA-insulin that can be safely administered to humans was determined to be 185 MBq. The use of [68Ga]Ga-NOTA-insulin as a PET radiotracer is safe and effective for observing brain uptake in vervet monkeys. Further, the Aptar CPS successfully targets [68Ga]Ga-NOTA-insulin to the brain. The data will be essential in guiding future studies of intranasal [68Ga]Ga-NOTA-insulin administration in humans.

Behavioral responses of vervet monkey Chlorocebus pygerythrus infants in a novel fostering program

ABSTRACT Vervet monkeys (Chlorocebus pygerythrus) are considered pests by farmers and homeowners. Consequent attempts to exterminate problem adult vervet monkeys often result in orphaned young offspring, which are sometimes taken to wildlife rehabilitation centers. We assessed the success of a novel fostering program at the Vervet Monkey Foundation, South Africa. Nine orphaned vervet monkeys were fostered to adult conspecific females of existing troops at the Foundation. The fostering protocol focused on reducing the time orphans spent in human rearing and involved a stepwise process of integration. We recorded the behaviors of orphans, including their interactions with their foster mother, to assess the process of fostering. Fostering success was high (89%). Orphans maintained close association with the foster mother and had little or no socio-negative and abnormal behavior. Comparison with literature showed a similar high fostering success in another vervet monkey study, regardless of the period and level of human-caregiving, and it is apparent that the duration of human care is less important than the protocol used for fostering. Nonetheless, our study has conservation relevance for vervet monkey rehabilitation.

The expression of type I and II gonadotropin-releasing hormone receptors transcripts in Vervet monkey (Chlorocebus aethiops) spermatozoa

Gonadotropin-Releasing Hormone (GnRH), acting via the GnRH receptor (GnRHR), and a member of G-protein coupled receptor (GPCR), plays an essential role in the control of reproduction while operating primarily at the hypothalamic level of the gonadotropic axis. GnRH and its receptor are co-expressed in certain specific cells, suggesting an autocrine regulation of such cells. In the male reproductive system, two forms of GnRH (I and II) and its receptors (GnRHR) are present in the human and non-human primate (NHP) testis, prostate, epididymis, seminal vesicle, and human spermatozoa. In humans, the GnRHR-II receptor gene is disrupted by a frameshift in exon 1 and a stop codon in exon 2, rendering the receptor non-functional, whereas a fully functional GnRHR-II receptor is present in New-World and Old-World monkeys. There is no evidence of the existence of a GnRH receptor in NHP sperm. Since the NHP has a phylogenetic relationship to man and is often used as models in reproductive physiology, this present study aimed to determine GnRHR-I and GnRHR-II in Vervet monkey (Chlorocebus aethiops) spermatozoa. A total of 24 semen samples were obtained from four adult Vervet monkeys through electro-ejaculation and utilized for genotyping and gene expression analysis of GnRHR-I and II. Here we report that both receptors were successfully identified in the Vervet monkey sperm with the abundance of GnRHR-I gene expression compared to GnRHR-II. In comparison to the human, there is no evidence of such a stop codon at position 179 in exon 2 of the Vervet GnRHR-II. These findings suggest that both receptors are transcriptionally functional in Vervet spermatozoa.

Protein expression of MEF2C during the critical period for visual development in vervet monkeys

During the early development of the visual cortex, there is a critical period when neuronal connections are highly sensitive to changes in visual input. Deprivation of visual stimuli during the critical period elicits robust anatomical and physiological rearrangements in the monkey visual cortex and serves as an excellent model for activity-dependent neuroplasticity. DNA microarray experiments were previously performed in our lab to analyze gene expression patterns in area V1 of vervet monkeys subjected to monocular deprivation (MD). An interesting candidate identified in its screen was myocyte enhancer-binding factor 2C (MEF2C), a transcription factor linked to neuronal survival. Consistent with the microarray data, we show that there is a qualitative increase in MEF2C protein expression in area V1 of infant as compared to adult vervet monkeys. Our results suggest that the regulation of neuronal survival is one of the molecular mechanisms underlying the critical period for visual cortical neuroplasticity.

Abstract P114: Cardiac and Renal Adrenergic Receptor Expression in Spontaneously Hypertensive Caribbean Vervets

Sympathetic nerve activity and adrenergic receptor stimulation causes development and maintenance of hypertension in patients and experimental animal models. The Caribbean vervet ( Chlorocebus aethiops sabaeus ), an Old World non-human primate, is a translational model of human cardiovascular disease due to its recent divergence, genetic similarity, upright posture, complex social structure, and diurnal behavior. Outbred and randomly selected adult Caribbean vervets exhibit systolic blood pressures (SBP) >140 mmHg in 36% of our cohort (124 of 345 individuals). We hypothesized that gene expression of adrenergic receptor subtypes in renal and cardiac tissue would be elevated in HT Caribbean vervets, and may contribute to spontaneous hypertension. Gene expression was measured using qRT-PCR and RQs compared using the Mann-Whitney U Test. HT animals (n=18, SBP: 168.24±7.25mmHg) had increased expression of both α- and β-adrenergic receptor subtypes in renal outer medulla (a 1a : NT RQ 1 ± 0.43 vs. HT RQ 2.26 ± 0.50, p<0.05; a 1d : NT RQ 1 ± 0.34 vs. HT RQ 2.25 ± 0.32, p<0.05; a 2a : NT RQ 1 ± 0.24 vs. HT RQ 1.92 ± 0.19, p<0.05; a 2c : NT RQ 1 ± 0.15 vs HT RQ 1.65 ± 0.15, p<0.05: β 1 : NT RQ 1 ± 0.24 vs. HT RQ 1.88 ± 0.18, p<0.05; and β 2 : NT RQ 1 ± 0.21 vs. HT RQ 1.87 ± 0.24, p<0.05) compared to NT animals (n=18, SBP: 96.61±3.2 mmHg). All α- and β 1 -adrenergic receptor expression in renal cortex and inner medulla was similar between the two groups. Inner medullary β 2 adrenergic receptor expression was elevated in HT animals (NT RQ 1 ± 0.25 vs HT RQ 1.62 ± 0.10, p<0.05). In the heart, β 1 adrenergic receptor expression was upregulated in the left ventricular myocardium of HT animals (NT RQ 1 ± 0.16 vs HT RQ 1.88 ± 0.35). Together, these data suggest that the HT Caribbean vervet may exhibit an exaggerated response to sympathetic nerve activity due to increased adrenergic receptor expression in the kidney and heart, which could contribute to the spontaneous hypertension observed in this translational large animal model.

Cannabinoid Receptors CB1 and CB2 Modulate the Electroretinographic Waves in Vervet Monkeys.

The expression patterns of the cannabinoid receptor type 1 (CB1R) and the cannabinoid receptor type 2 (CB2R) are well documented in rodents and primates. In vervet monkeys, CB1R is present in the retinal neurons (photoreceptors, horizontal cells, bipolar cells, amacrine cells, and ganglion cells) and CB2R is exclusively found in the retinal glia (Müller cells). However, the role of these cannabinoid receptors in normal primate retinal function remains elusive. Using full-field electroretinography in adult vervet monkeys, we recorded changes in neural activity following the blockade of CB1R and CB2R by the intravitreal administration of their antagonists (AM251 and AM630, resp.) in photopic and scotopic conditions. Our results show that AM251 increases the photopic a-wave amplitude at high flash intensities, whereas AM630 increases the amplitude of both the photopic a- and b-waves. In scotopic conditions, both blockers increased the b-wave amplitude but did not change the a-wave amplitude. These findings suggest an important role of CB1R and CB2R in primate retinal function.

Osteoarthritic changes in vervet monkey knees correlate with meniscus degradation and increased matrix metalloproteinase and cytokine secretion

Meniscus injury increases osteoarthritis risk but its pathobiology in osteoarthritis is unclear. We hypothesized that older adult vervet monkeys would exhibit knee osteoarthritic changes and the degenerative menisci from these animals would secrete matrix metalloproteinases (MMPs) and pro-inflammatory cytokines that contribute to the development of osteoarthritis. In a cross sectional analysis of healthy young adult (9-12 years) and old (19-26 years) adult female vervet monkeys, knees were evaluated in vivo with computed tomography (CT) imaging, and joint tissues were morphologically graded at necropsy. Meniscus explants were subsequently cultured to evaluate meniscal MMP and cytokine secretion. CT images revealed significant bony osteoarthritic changes in 80% of older monkeys which included increases in osteophyte number and meniscal calcification. Meniscus and cartilage degradation scores were greater in the older monkeys and were positively correlated (r > 0.7). Menisci from older animals exhibiting osteoarthritic changes secreted significantly more MMP-1, MMP-3, and MMP-8 than healthy menisci from younger monkeys. Older menisci without significant osteoarthritic changes secreted more IL-7 than healthy young menisci while older osteoarthritic menisci secreted more IL-7 and granulocyte-macrophage colony-stimulating factor than healthy older menisci. Aged vervets develop naturally occurring knee osteoarthritis that includes involvement of the meniscus. Degenerative menisci secreted markedly increased amounts of matrix-degrading enzymes and inflammatory cytokines. These factors would be expected to act on the meniscus tissue and local joint tissues and may ultimately promote osteoarthritis development. These finding also suggest vervet monkeys are a useful animal model for studying the progression of osteoarthritis.

Age-related structural changes in upper extremity muscle tissue in a nonhuman primate model

Longitudinal studies of upper extremity aging in humans include logistical concerns that animal models can overcome. The vervet is a promising species with which to study aging-related processes. However, age-related changes in upper extremity muscle structure have not been quantified in this species. This study measured age-related changes to muscle structure, examined relationships between muscle structure and measures of physical performance, and evaluated the presence of rotator cuff tears. Muscle structure (volume, optimal fiber length, and physiologic cross-sectional area (PCSA)) of 10 upper extremity muscles was quantified from the right upper limb of 5 middle-aged and 6 older adult female vervets. Total measured PCSA was smaller (P=.001) in the older adult vervets than in the middle-aged vervets. Muscle volume reduction predominate the age-related reductions in PCSA. Total measured PCSA was not correlated to any measures of physical performance. No rotator cuff tears were observed. Supraspinatus volume was relatively larger and deltoid volume relatively smaller in the vervet compared with a human. The vervet is an appropriate translational model for age-related upper extremity muscle volume loss. Functional measures were not correlated to PCSA, suggesting the vervets may have enough strength for normal function despite loss of muscle tissue. Reduced relative demand on the supraspinatus may be responsible for the lack of naturally occurring rotator cuff tears.

Adult age confounds estimates of static allometric slopes in a vertebrate

In many animal groups, the size of male genitalia scales shallowly with individual body size. This widespread pattern appears to admit some exceptions. For instance, steep allometries have been reported for vertebrate genitalia. This exception, however, may be due to a confounding effect arising from the continued growth of some structures during adulthood in vertebrates. Consider the possibility that genitalia continue to grow in adults while body size does not. If so, taking measurements from adults of different ages could yield steeper allometries than would be obtained from measurements of adults of the same age. We used vervet monkeys to test this hypothesis. We found that all body parts continued to grow in adult vervet monkeys, with sexual traits (including genitalia) showing faster growth rates. Traits with faster growth rates over adult ages had steeper allometries. And accounting for variation in adult age yielded shallower allometries, bringing vervet monkey genitalia in line with the predominant pattern observed in other animal groups. These results suggest that steep allometric slope estimates reported for other vertebrates may be due in part to mixing of adult ages, and reinforces one of the most consistent patterns yet detected in the study of static allometry.

Abstract 412: A Unique Telemetric Method for Long-term Measurement of Blood Pressures and Core Body Temperature in Hypertensive and Normotensive Non-human Primates

A non-human primate model of essential hypertension has unequivocal potential for understanding mechanisms of disease but requires a unique method for telemetric blood pressure measurement in animals living within a habituated natural environment. We have now identified a unique non-human primate model of spontaneous, essential hypertension in Chlorocebus aethiops sabaeus, the African Green, or vervet, monkey. Using forearm plethysmography under light ketamine sedation (~15mg/kg), adult vervets were categorized as hypertensive (HT; SBP >140mmHg), borderline hypertensive (BHT; 120mmHg < SBP < 140mmHg), or normotensive (NT; SBP < 120 mmHg). Of the 168 males phenotyped, 32% (53 of 168) were HT (average SBP = 168.79±3.29mmHg), 27% (45 of 168) were BHT (average SBP = 129.58±0.88mmHg), and 41% (70 of 168) were NT (average SBP = 100.21±1.65mmHg). Stellar Telemetry solid-state pressure sensors were surgically implanted into the abdominal aorta of feral, male monkeys (Chlorocebus sabaeus aethiops). SBP, diastolic (DBP) and mean (MBP) arterial pressures, core body temperature and heart rate were determined using different data acquisition parameters to assess system precision and reliability in this physically active non-human primate with spontaneous essential hypertension. All animals were pre-phenotyped for blood pressure using forearm plethysmography under light ketamine anesthesia. Different recording parameters (n=4) yielded consistent BPs, in normotensive (MBP=104±4.35 mmHg) and hypertensive (MBP=126±7.57 mmHg) animals. Ultrasonographic examination documented effective sensor placement directly within the vessel lumen. Post implant necropsy revealed no sensor induced blood pathologies. Conscious, telemetered SBPs were consistent with those of monkeys measured using plethysmography. This model of hypertension in an Old World, non-human primate is translational to human essential hypertension and allows for new directions in a genetically similar species. The use of the Stellar Telemetry system is ideal for monitoring conscious blood pressure, heart rate and body temperature in active primates allowing for cardiovascular assessment during natural social interactions and species specific behaviors.

Abstract 219: Altered Renal and Cardiac Morphology in a Non-Human Primate Model of Spontaneous Essential Hypertension

Current models of essential hypertension are limited in comparisons to human pathophysiology due to distinct differences in postural positioning, circadian rhythmicity, and genetic variation. We have identified a unique non-human primate model of spontaneous, essential hypertension in Chlorocebus aethiops sabaeus , the African Green, or vervet, monkey. Using forearm plethysmography under light ketamine sedation (~15mg/kg), adult vervets were categorized as hypertensive (HT; SBP >140mmHg), borderline hypertensive (BHT; 120mmHg < SBP < 140mmHg), or normotensive (NT; SBP < 120 mmHg). Of the 168 males phenotyped, 32% (53 of 168) were HT (average SBP = 168.79±3.29mmHg), 27% (45 of 168) were BHT (average SBP = 129.58±0.88mmHg), and 41% (70 of 168) were NT (average SBP = 100.21±1.65mmHg). In a smaller study of 18 adult females, 1 was found to be HT (SBP = 156mmHg), 2 were BHT (average SBP = 134±2.0mmHg), and 15 were NT (average SBP = 98.06±4.32mmHg). Fixed paraffin-embedded histological sections of vervet cardiac (H&E) and renal (periodic acid Schiff) tissues were digitized and analyzed. Wall/lumen ratios of renal arterioles (average diameter 33.01±0.5μm) were greater in HT (0.33±0.03) compared to NT (0.24±0.01) male monkeys. Bowman’s capsule space was increased in HT (43.14±3.98% area) glomeruli compared to NT (29.92±2.42% area) glomeruli (p<0.05). Indicative of left ventricular hypertrophy, left ventricular cells were decreased in HT (1833.33±65.48 cells/mm 2 ) compared to NT monkeys (2223.61±59.72 cells/mm 2 ; p<0.05). The increased wall/lumen ratios and Bowman’s capsular spaces indicate that renal vascular hypertrophy and glomerular damage occur in this non-human primate model of essential hypertension. Left ventricular hypertrophy combined with renal glomerular and vascular dysfunction provides strong evidence for using this non-human primate model as a translational experimental species.

Muscle Heat Shock Protein 70 Predicts Insulin Resistance With Aging

Heat shock protein 70 (HSP70) protects cells from accumulating damaged proteins and age-related functional decline. We studied plasma and skeletal muscle (SkM) HSP70 levels in adult vervet monkeys (life span ≈ 25 years) at baseline and after 4 years (≈10 human years). Insulin, glucose, homeostasis model assessment scores, triglycerides, high-density lipoprotein and total plasma cholesterol, body weight, body mass index, and waist circumference were measured repeatedly, with change over time estimated by individual regression slopes. Low baseline SkM HSP70 was a proximal marker for developing insulin resistance and was seen in monkeys whose insulin and homeostasis model assessment increased more rapidly over time. Changes in SkM HSP70 inversely correlated with insulin and homeostasis model assessment trajectories such that a positive change in SkM level was beneficial. The strength of the relationship between changes in SkM HSP70 and insulin remained unchanged after adjustment for all covariates. Younger monkeys drove these relationships, with HSP70 alone being predictive of insulin changes with aging. Plasma and SkM HSP70 were unrelated and HSP70 release from peripheral blood mononuclear cells was positively associated with insulin concentrations in contrast to SkM. Results from aged humans confirmed this positive association of plasma HSP70 and insulin. In conclusion, higher levels of SkM HSP70 protect against insulin resistance development during healthy aging.

Dose-response inhibitory effects of purified cathinone from khat (Catha edulis) on cortisol and prolactin release in vervet monkeys (Chlorocebus aethiops)

This study reports acute and sub-chronic effects of cathinone on hormonal alterations in single-caged vervet monkeys. Fourteen adult vervet monkeys were used, 12 of which were treated and 2 controls. Pre-treatment phase of 1month aimed at establishing baseline levels of hormones while treatment phase of 4months considered the dose- and time-response effects of cathinone on serum cortisol and prolactin levels. Test animals were allocated four groups of three animals each and administered 0.8, 1.6, 3.2 and 6.4mg/kg body weight of cathinone orally while controls were administered normal saline. Treatment was done at alternate days of each week. Serum prolactin and cortisol immunoassays were done. Hormonal data was analysed by repeated measures ANCOVA. Results indicate a dose [F (4, 8) = 218, P < 0.001] and time [F (18, 142) = 21.7, P < 0.001] dependent effect of cathinone on cortisol levels with a significant dose by week interaction [F (71, 142) = 4.86, P < 0.001]. Similarly, there was a decrease in serum prolactin [F (4, 8) = 267, P < 0.001] with escalating doses of cathinone with a significant dose x week interaction [F (59, 118) = 13.03, P < 0.001]. The findings demonstrate that at high doses and long-term exposure, cathinone causes hormonal alterations probably via changes in hypothalamo-hypophyseo-adrenocortical and gonadal axes integrity.

Acute and sub-chronic effects of purified cathinone from khat (Catha edulis) on behavioural profiles in vervet monkeys (Chlorocebus aethiops)

We investigated the cumulative effects of cathinone on behavioural alterations in single-caged vervet monkeys. Fourteen adult vervets were divided into tests (12 animals) and controls (2 animals), and exposed to escalating doses of cathinone at alternate days of each week for 4months in presence and absence of cage enrichment. One month of pre-treatment phase served to establish baseline values. Composite behavioural scores of aggression, anxiety, abnormal responses, withdrawal and appetite loss were done. A series of repeated measures analysis of variances were conducted to examine the extent to which cathinone administration was associated with patterns of changes in behavioural data. Results indicate a dose-dependent effect of cathinone on increases of aggression, anxiety, abnormal responses, withdrawal, and appetite loss. The findings demonstrate that at high doses and long-term exposure, cathinone causes behavioural alterations probably via changes in presynaptic striatal dopamine system.

IL-6 is Upregulated in Late-Stage Disease in Monkeys Experimentally Infected withTrypanosoma brucei rhodesiense

The management of human African trypanosomiasis (HAT) is constrained by lack of simple-to-use diagnostic, staging, and treatment tools. The search for novel biomarkers is, therefore, essential in the fight against HAT. The current study aimed at investigating the potential of IL-6 as an adjunct parameter for HAT stage determination in vervet monkey model. Four adult vervet monkeys (Chlorocebus aethiops) were experimentally infected with Trypanosoma brucei rhodesiense and treated subcuratively at 28 days after infection (dpi) to induce late stage disease. Three noninfected monkeys formed the control group. Cerebrospinal fluid (CSF) and blood samples were obtained at weekly intervals and assessed for various biological parameters. A typical HAT-like infection was observed. The late stage was characterized by significant (P < 0.05) elevation of CSF IL-6, white blood cell count, and total protein starting 35 dpi with peak levels of these parameters coinciding with relapse parasitaemia. Brain immunohistochemical staining revealed an increase in brain glial fibrillary acidic protein expression indicative of reactive astrogliosis in infected animals which were euthanized in late-stage disease. The elevation of IL-6 in CSF which accompanied other HAT biomarkers indicates onset of parasite neuroinvasion and show potential for use as an adjunct late-stage disease biomarker in the Rhodesian sleeping sickness.

Myosin heavy chain isoform expression in the Vastus Lateralis muscle of aging African green vervet monkeys

Non-human primates (NHP) represent an emerging animal model for the study of physical function, and provide opportunities for exploration of relationships of muscle biomolecular changes with age. One such primate model, the African green vervet monkey, has been used extensively in biomedical research but little is known regarding skeletal muscle composition, expression of myosin heavy chain (MHC) isoforms, and changes with age. In the present study we examined the effects of age on vastus lateralis (VL) muscle fiber-type composition, fiber cross-sectional area (CSA), and MHC isoforms expressed in 4 young and 4 older adult vervet monkeys. Proteomics analysis, using a human and nonhuman primate protein database, showed five MHC isoforms (I, IIA, IIX, IIB, and IIB′) expressed in female vervet VL muscle, which matched the human MHC isoforms. Fast type II fibers predominated and no pure type IIB or IIB’ containing fibers were detected. Hybrid fibers containing IIB/IIB’ MHC decreased in the old vervets. The CSA of both type I and type II fibers was significantly smaller in older vervet while type IIA fibers showed the most severity of atrophy. The decrease of fast MHC and atrophy of muscle fiber with aging recapitulate observations in human VL muscle. These findings, along with its homology of MHC between the vervet and human suggested that the vervet monkey may be a suitable preclinical model for understanding the cellular and molecular basis of sarcopenia and for developing new interventions to ameliorate the impact of disorders that affect skeletal muscle structure and function.

The effect of housing and environmental enrichment on stereotyped behavior of adult vervet monkeys (Chlorocebus aethiops)

Little information is available on the response of vervet monkeys to different housing conditions or on the suitability of enrichment devices or methods for vervet monkeys. In this study, the authors evaluated the occurrence of stereotyped behavior in adult vervet monkeys under various conditions of housing and enrichment. The variables included cage size, cage level (upper or lower), enrichment with a foraging log, enrichment with an exercise cage and presence of a mate. The authors first determined the incidence of stereotyped behavior in captive-bred, singly housed adult female and male vervet monkeys. They then exposed monkeys to different housing and enrichment situations and compared the incidence of stereotyped behavior among the monkeys. The authors found that more females than males engaged in stereotyped behavior and that females, on average, engaged in such behavior for longer periods of time than males. Stereotyped behavior was most often associated with a small, single cage. The average amount of observed stereotyped activity in monkeys housed in a small cage was significantly lower when the monkeys had access to either a foraging log or an exercise cage. Stereotyped behavior was also lower in female monkeys that were housed (either with a male or without a male) in a larger cage. The least amount of abnormal behavior was associated with the largest, most complex and enriched housing situation. Males and females housed in cages on the lower level of two-level housing engaged in more stereotyped behavior than did monkeys housed in the upper level, regardless of the presence or type of enrichment provided.

Host Response to Human Acellular Dermal Matrix Transplantation in a Primate Model of Abdominal Wall Repair

Commercially available human acellular dermal matrix (HADM), AlloDerm((R)), was implanted as an interpositional graft in the abdominal wall of adult vervet monkeys. Host response to implanted HADM was evaluated and compared with a human cellular dermal matrix (HCDM) and a primate acellular dermal matrix (PADM). Clinical acceptance of the acellular grafts (HADM and PADM) and graft remodeling were evidenced by fibroblast repopulation and neoangiogenesis. A mild inflammatory response marked predominantly by macrophages and T-cells was present in both HADM and PADM during the first month but was absent by 3 months. Similarly, antibody and complement deposition into the grafts as well as in the serum was evident only at the early time points. Interleukin-6 (IL-6) or IL-10 was induced in some acellular graft-implanted monkeys at the early time points, but tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), or IL-2 was not detected over the study period. In contrast, significant inflammation was observed in HCDM-implanted animals, as evidenced by immune cell infiltration (p </= 0.0001), immunoglobulin G (IgG) binding (p < 0.001), complement (C5b) deposition (p < 0.05), TNF-alpha deposition (p < 0.001), and macrophage activation (p < 0.05). Abdominal wall repair in the vervet monkey is an immunologically relevant model to evaluate functional efficacy and host immune response to implanted biomaterials and may be predictive of clinical response and surgical outcomes in humans.

Jill D. E. Pruetz (ed): The Socioecology of Adult Female Patas Monkeys and Vervets in Kenya

Jill D. E. Pruetz (ed): The Socioecology of Adult Female Patas Monkeys and Vervets in Kenya

Architectonic distribution of the serotonin transporter within the orbitofrontal cortex of the vervet monkey

To elucidate the organization of the serotoninergic innervation within the orbitofrontal cortex (OFC), serotonin transporter (SERT) density was quantified by autoradiography using [ 3H]cyanoimipramine binding. In six adult vervet monkeys, 15 architectonic areas were delineated according to cytoarchitectonic (Nissl), myeloarchitectonic (Gallyas) and chemoarchitectonic (acetylcholinesterase) criteria to assess SERT distribution at two levels of organization: cortical area and cortical type. For cortical type, the 15 areas were evenly divided into three different categories primarily based upon the degree of granularization of layer IV: agranular, dysgranular, and granular. Within agranular and dysgranular, but not granular cortical types, SERT density was area-specific and progressively decreased in a medial to lateral gradient. Across cortical types, SERT density decreased in a caudal to rostral gradient: agranular>dysgranular>granular. A similar caudal to rostral gradient was seen when serotonin content was measured (using high performance liquid chromatography) in areas representative of each cortical type. Collectively, these results suggest that the serotoninergic innervation is organized according to both cortical type and area, and is thus structured to differentially modulate information processing within the OFC.