Plasma and CSF biomarkers of aging and cognitive decline in Caribbean vervets.

INTRODUCTION: Vervets are non-human primates that share high genetic homology with humans and develop amyloid beta (Aß) pathology with aging. We expand current knowledge by examining Aß pathology, aging, cognition, and biomarker proteomics. METHODS: Amyloid immunoreactivity in the frontal cortex and temporal cortex/hippocampal regions from archived vervet brain samples ranging from young adulthood to old age was quantified. We also obtained cognitive scores, plasma samples, and cerebrospinal fluid (CSF) samples in additional animals. Plasma and CSF proteins were quantified with platforms utilizing human antibodies. RESULTS: We found age-related increases in Aß deposition in both brain regions. Bioinformatic analyses assessed associations between biomarkers and age, sex, cognition, and CSF Aß levels, revealing changes in proteins related to immune-related inflammation, metabolism, and cellular processes. DISCUSSION: Vervets are an effective model of aging and early-stage Alzheimer's disease, and we provide translational biomarker data that both align with previous results in humans and provide a basis for future investigations. HIGHLIGHTS: We found changes in immune and metabolic plasma biomarkers associated with age and cognition. Cerebrospinal fluid (CSF) biomarkers revealed changes in cell signaling indicative of adaptative processes. TNFRSF19 (TROY) and Artemin co-localize with Alzheimer's disease pathology. Vervets are a relevant model for translational studies of early-stage Alzheimer's disease.

Effect of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide on alcohol consumption in alcohol-preferring male vervet monkeys.

RATIONALE: Glucagon-like peptide-1 (GLP-1) receptor agonists reduce alcohol consumption in rodents and non-human primates. Semaglutide is a new long-acting GLP-1 receptor agonist, widely used in the clinic against type 2 diabetes and obesity. It is also reported to reduce alcohol intake in rodents. OBJECTIVES: This study investigates the possible inhibitory effect of semaglutide on alcohol intake in alcohol-preferring African green monkeys. METHODS: We performed a vehicle-controlled study on male monkeys that had demonstrated a preference for alcohol. In the monkeys selected for voluntary alcohol drinking, alcohol consumption was measured for ten days at baseline (Monday to Friday for two weeks). During this period, the monkeys had access to alcohol 4 h per day and free access to water 24 h per day. After two weeks of baseline measurements, the monkeys were randomized to semaglutide or vehicle. Each group consisted of ten monkeys, and the two groups were balanced with respect to baseline alcohol intake. Following the baseline period, the monkeys were treated with escalating doses of semaglutide (up to 0.05 mg/kg) or vehicle subcutaneously twice weekly for two weeks during which period alcohol was not available. After uptitration, the monkeys had access to alcohol 4 h daily for 20 days (Monday to Friday for 4 weeks), and alcohol consumption was measured. During this alcohol exposure period, treatment with semaglutide (0.05 mg/kg twice weekly) or vehicle continued for three weeks followed by a one-week washout period. RESULTS: Compared to the vehicle, semaglutide significantly reduced alcohol intake. There were no signs of emetic events or changes in water intake. CONCLUSIONS: These data demonstrate for the first time the potent effect of semaglutide in reducing voluntary alcohol intake in non-human primates and further substantiate the need for clinical trials investigating the effect of semaglutide in patients with alcohol-use disorder.

miRNA Expression Analysis of the Hippocampus in a Vervet Monkey Model of Fetal Alcohol Spectrum Disorder Reveals a Potential Role in Global mRNA Downregulation.

MicroRNAs (miRNAs) are short-length non-protein-coding RNA sequences that post-transcriptionally regulate gene expression in a broad range of cellular processes including neuro- development and have previously been implicated in fetal alcohol spectrum disorders (FASD). In this study, we use our vervet monkey model of FASD to follow up on a prior multivariate (developmental age × ethanol exposure) mRNA analysis (GSE173516) to explore the possibility that the global mRNA downregulation we observed in that study could be related to miRNA expression and function. We report here a predominance of upregulated and differentially expressed miRNAs. Further, the 24 most upregulated miRNAs were significantly correlated with their predicted targets (Target Scan 7.2). We then explored the relationship between these 24 miRNAs and the fold changes observed in their paired mRNA targets using two prediction platforms (Target Scan 7.2 and miRwalk 3.0). Compared to a list of non-differentially expressed miRNAs from our dataset, the 24 upregulated and differentially expressed miRNAs had a greater impact on the fold changes of their corresponding mRNA targets across both platforms. Taken together, this evidence raises the possibility that ethanol-induced upregulation of specific miRNAs might contribute functionally to the general downregulation of mRNAs observed by multiple investigators in response to prenatal alcohol exposure.

Age and Sex-Related Changes in Retinal Function in the Vervet Monkey.

Among the deficits in visual processing that accompany healthy aging, the earliest originate in the retina. Moreover, sex-related differences in retinal function have been increasingly recognized. To better understand the dynamics of the retinal aging trajectory, we used the light-adapted flicker electroretinogram (ERG) to functionally assess the state of the neuroretina in a large cohort of age- and sex-matched vervet monkeys (N = 35), aged 9 to 28 years old, with no signs of obvious ocular pathology. We primarily isolated the cone-bipolar axis by stimulating the retina with a standard intensity light flash (2.57 cd/s/m2) at eight different frequencies, ranging from 5 to 40 Hz. Sex-specific changes in the voltage and temporal characteristics of the flicker waveform were found in older individuals (21-28 years-old, N = 16), when compared to younger monkeys (9-20 years-old, N = 19), across all stimulus frequencies tested. Specifically, significantly prolonged implicit times were observed in older monkeys (p < 0.05), but a significant reduction of the amplitude of the response was only found in old male monkeys (p < 0.05). These changes might reflect ongoing degenerative processes targeting the retinal circuitry and the cone subsystem in particular. Altogether, our findings corroborate the existing literature in humans and other species, where aging detrimentally affects photopic retinal responses, and draw attention to the potential contribution of different hormonal environments.

Dose-Related Reduction in Hippocampal Neuronal Populations in Fetal Alcohol Exposed Vervet Monkeys.

Fetal alcohol spectrum disorder (FASD) is a chronic debilitating condition resulting in behavioral and intellectual impairments and is considered the most prevalent form of preventable mental retardation in the industrialized world. We previously reported that 2-year-old offspring of vervet monkey (Chlorocebus sabeus) dams drinking, on average, 2.3 ± 0.49 g ethanol per Kg maternal body weight 4 days per week during the last third of pregnancy had significantly lower numbers of CA1 (-51.6%), CA2 (-51.2%) and CA3 (-42.8%) hippocampal neurons, as compared to age-matched sucrose controls. Fetal alcohol-exposed (FAE) offspring also showed significantly lower volumes for these structures at 2 years of age. In the present study, we examined these same parameters in 12 FAE offspring with a similar average but a larger range of ethanol exposures (1.01-2.98 g/Kg/day; total ethanol exposure 24-158 g/Kg). Design-based stereology was performed on cresyl violet-stained and doublecortin (DCX)-immunostained sections of the hippocampus. We report here significant neuronal deficits in the hippocampus with a significant negative correlation between daily dose and neuronal population in CA1 (r2 = 0.486), CA2 (r2 = 0.492), and CA3 (r2 = 0.469). There were also significant correlations between DCX population in the dentate gyrus and daily dose (r2 = 0.560). Both correlations were consistent with linear dose-response models. This study illustrates that neuroanatomical sequelae of fetal ethanol exposure are dose-responsive and suggests that there may be a threshold for this effect.

mRNA expression analysis of the hippocampus in a vervet monkey model of fetal alcohol spectrum disorder.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) are common, yet preventable developmental disorders that stem from prenatal exposure to alcohol. This exposure leads to a wide array of behavioural and physical problems with a complex and poorly defined biological basis. Molecular investigations to date predominantly use rodent animal models, but because of genetic, developmental and social behavioral similarity, primate models are more relevant. We previously reported reduced cortical and hippocampal neuron levels in an Old World monkey (Chlorocebus sabaeus) model with ethanol exposure targeted to the period of rapid synaptogenesis and report here an initial molecular study of this model. The goal of this study was to evaluate mRNA expression of the hippocampus at two different behavioural stages (5 months, 2 years) corresponding to human infancy and early childhood. METHODS: Offspring of alcohol-preferring or control dams drank a maximum of 3.5 g ethanol per kg body weight or calorically matched sucrose solution 4 days per week during the last 2 months of gestation. Total mRNA expression was measured with the Affymetrix GeneChip Rhesus Macaque Genome Array in a 2 × 2 study design that interrogated two independent variables, age at sacrifice, and alcohol consumption during gestation. RESULTS AND DISCUSSION: Statistical analysis identified a preferential downregulation of expression when interrogating the factor 'alcohol' with a balanced effect of upregulation vs. downregulation for the independent variable 'age'. Functional exploration of both independent variables shows that the alcohol consumption factor generates broad functional annotation clusters that likely implicate a role for epigenetics in the observed differential expression, while the variable age reliably produced functional annotation clusters predominantly related to development. Furthermore, our data reveals a novel connection between EFNB1 and the FASDs; this is highly plausible both due to the role of EFNB1 in neuronal development as well as its central role in craniofrontal nasal syndrome (CFNS). Fold changes for key genes were subsequently confirmed via qRT-PCR. CONCLUSION: Prenatal alcohol exposure leads to global downregulation in mRNA expression. The cellular interference model of EFNB1 provides a potential clue regarding how genetically susceptible individuals may develop the phenotypic triad generally associated with classic fetal alcohol syndrome.

FGF21 suppresses alcohol consumption through an amygdalo-striatal circuit.

Excessive alcohol consumption is a major health and social issue in our society. Pharmacologic administration of the endocrine hormone fibroblast growth factor 21 (FGF21) suppresses alcohol consumption through actions in the brain in rodents, and genome-wide association studies have identified single nucleotide polymorphisms in genes involved with FGF21 signaling as being associated with increased alcohol consumption in humans. However, the neural circuit(s) through which FGF21 signals to suppress alcohol consumption are unknown, as are its effects on alcohol consumption in higher organisms. Here, we demonstrate that administration of an FGF21 analog to alcohol-preferring non-human primates reduces alcohol intake by 50%. Further, we reveal that FGF21 suppresses alcohol consumption through a projection-specific subpopulation of KLB-expressing neurons in the basolateral amygdala. Our results illustrate how FGF21 suppresses alcohol consumption through a specific population of neurons in the brain and demonstrate its therapeutic potential in non-human primate models of excessive alcohol consumption.

The Influence of Tobacco Smoke/Nicotine on CYP2A Expression in Human and African Green Monkey Lungs.

CYP2A enzymes metabolically inactivate nicotine and activate tobacco-derived procarcinogens [e.g., 4-[methylnitrosamino]-1-(3-pyridyl)-1-butanone]. Smoking decreases nicotine clearance, and chronic nicotine reduces hepatic CYP2A activity. However, little is known about the impact of smoking or nicotine on the expression of CYP2A in the lung. We investigated 1) the levels of human lung CYP2A mRNA in smokers versus nonsmokers and 2) the impact of daily nicotine treatment on lung CYP2A protein levels in African green monkeys (AGMs). Lung CYP2A13, CYP2A6, and CYP2A7 (and CYP1A2) mRNA levels in smokers and nonsmokers were assessed in Gene Expression Omnibus data sets (GSE30063, GSE108134, and GSE11784). The impact of chronic, twice-daily, subcutaneous nicotine at two doses (0.3 and 0.5 mg/kg) versus vehicle on lung CYP2A protein levels was assessed. The impact of ethanol self-administration was also investigated, with and without nicotine treatment. Smokers versus nonsmokers (from GSE30063 and GSE108134) had lower (1.04- to 1.12-fold) levels of lung CYP2A13, CYP2A6, and CYP2A7 (and higher CYP1A2) mRNA. Both doses of nicotine tested decreased AGM lung CYP2A protein (3- to 7-fold). Ethanol self-administration had no effect on AGM lung CYP2A protein, and there was no interaction between ethanol and nicotine. Our results suggest that smoking was associated with a reduction in human lung CYP2A13, CYP2A6, and CYP2A7 mRNA, consistent with the role of nicotine treatment in reducing AGM lung CYP2A protein. This regulation by smoking/nicotine will increase interindividual variation in lung CYP2A levels, which may impact the localized metabolism of inhaled drugs and tobacco smoke procarcinogens. SIGNIFICANCE STATEMENT: CYP2A13 and CYP2A6 are expressed in the lung and may contribute to local procarcinogen activation. Smokers had lower lung CYP2A mRNA levels compared with nonsmokers. Lung CYP2A protein expression was decreased by systemic treatment with nicotine. Decreased lung CYP2A expression may alter smoking-related lung cancer risk and tissue damage from other inhaled toxins. This novel regulatory impact of nicotine, including nicotine found in smoking-cessation nicotine-replacement therapies, may have potential benefits on smoking-related lung cancer risk.

Transient receptor potential vanilloid type 1 is expressed in the horizontal pathway of the vervet monkey retina.

The ubiquitous distribution of the classic endocannabinoid system (cannabinoid receptors CB1 and CB2) has been demonstrated within the monkey nervous system, including the retina. Transient receptor potential vanilloid type 1 (TRPV1) is a cannabinoid-like non-selective cation channel receptor that is present in the retina and binds to endovannilloids and endocannabinoids, like anandamide, 2-arachidonoylglycerol and N-arachidonoyl dopamine. Retinal expression patterns of TRPV1 are available for rodents and data in higher mammals like humans and monkeys are scarce. We therefore thoroughly examined the expression and localization of TRPV1 in the retina, at various eccentricities, of the vervet (Chlorocebus sabeus) monkey, using Western blots and immunohistochemistry. Our results demonstrate that TRPV1 is found mainly in the outer and inner plexiform layers, and in the retinal ganglion cell (RGC) layer with a higher density in the periphery. Co-immunolabeling of TRPV1 with parvalbumin, a primate horizontal cell marker, revealed a clear overlap of expression throughout the entire cell structure with most prominent staining in the cell body membrane and synaptic terminals. Furthermore, double labeling of TRPV1 and syntaxin was found throughout amacrine cells in the inner plexiform layer. Finally, double staining of TRPV1 and Brn3a allowed us to confirm its previously reported expression in the cell bodies and dendrites of RGCs. The presence of TRPV1 in the horizontal pathway suggests a function of this receptor in lateral inhibition between photoreceptors through the horizontal cells, and between bipolar cells through amacrine cells.

Leptospira Infection in African Green Monkeys in an Endemic Area: An Opportunity for Comparative Studies in a Natural Environment.

This study was performed to investigate the potential asymptomatic Leptospira reservoir status among African green monkeys (AGMs) in the Caribbean island of Saint Kitts, and whether there is any renal pathology associated with Leptospira exposure. Forty-eight percent of AGMs tested were positive for Leptospira antibodies by the microscopic agglutination test. Leptospira DNA was detected in 4% of kidney samples tested using a lipl32 gene based PCR. We observed minimal to severe microscopic renal lesions in 85% of the AGM kidneys evaluated. The majority of the AGMs (n = 26) had only minimal to mild interstitial nephritis and a few (n = 3) had moderate to severe lesions. The presence of interstitial nephritis was not significantly associated with Leptospira exposure. The presence of infected AGMs in a small surface limited geographic region may pose zoonotic threat to humans and animals. The impact of Leptospira infection in renal pathology in AGMs warrants further investigation. AGMs residing in a natural setting in an insular, surface limited Leptospira endemic geographic region may offer opportunities for comparative studies to advance the field of leptospirosis. Due to their similarity to humans, such studies in AGMs may also provide translational opportunities to advance Leptospira research.

l-Serine Reduces Spinal Cord Pathology in a Vervet Model of Preclinical ALS/MND.

The early neuropathological features of amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) are protein aggregates in motor neurons and microglial activation. Similar pathology characterizes Guamanian ALS/Parkinsonism dementia complex, which may be triggered by the cyanotoxin ß-N-methylamino-l-alanine (BMAA). We report here the occurrence of ALS/MND-type pathological changes in vervets (Chlorocebus sabaeus; n = 8) fed oral doses of a dry powder of BMAA HCl salt (210 mg/kg/day) for 140 days. Spinal cords and brains from toxin-exposed vervets were compared to controls fed rice flour (210 mg/kg/day) and to vervets coadministered equal amounts of BMAA and l-serine (210 mg/kg/day). Immunohistochemistry and quantitative image analysis were used to examine markers of ALS/MND and glial activation. UHPLC-MS/MS was used to confirm BMAA exposures in dosed vervets. Motor neuron degeneration was demonstrated in BMAA-dosed vervets by TDP-43+ proteinopathy in anterior horn cells, by reactive astrogliosis, by activated microglia, and by damage to myelinated axons in the lateral corticospinal tracts. Vervets dosed with BMAA + l-serine displayed reduced neuropathological changes. This study demonstrates that chronic dietary exposure to BMAA causes ALS/MND-type pathological changes in the vervet and coadministration of l-serine reduces the amount of reactive gliosis and the number of protein inclusions in motor neurons.

Retinal structure and function in monkeys with fetal alcohol exposure.

Exposure to ethanol in utero leads to several brain development disorders including retinal abnormalities whose underlying cellular pathogenesis remains elusive. We recently reported that fetal alcohol exposure (FAE) in vervet monkeys induces anomalies of full-field electroretinogram (ERG) waveforms that suggest premature aging of the retina. The goal of this study is to characterize the anatomo-functional mechanisms underlying the retinal changes observed in fetal alcohol exposed (FAE) monkeys, and age- and sex-matched normals. First, we examined in vivo the fundus of the eyes, measured intraocular pressure (IOP) and assessed cone activity using flicker ERG. Second, we investigated ex vivo, protein expression and anatomical organization of the retina using Western blotting, classical histology and immunohistochemistry. Our results indicated that the fundus of the eyes showed both, increased vascularization (tessellated fundus) and IOP in FAE monkeys. Furthermore, light-adapted flicker responses above 15 Hz were also significantly higher in FAE monkeys. Although there were no obvious changes in the overall anatomy in the FAE retina, Glial Fibrillary Acidic Protein (GFAP, a potent marker of astrocytes) immunoreactivity was increased in the FAE retinal ganglion cell layer indicating a strong astrogliosis. These alterations were present in juvenile (2 years old) monkeys and persist in adults (8 years old). Moreover, using specific cell type markers, no significant modifications in the morphology of the photoreceptors, horizontal cells, bipolar cells, and amacrine cells were observed. Our data indicate that FAE does indeed induce anatomical changes within the retinal ganglion cell layer that are reflected in the increased photosensitivity of the cone photoreceptors.

Perinatal MAO Inhibition Produces Long-Lasting Impairment of Serotonin Function in Offspring.

In addition to transmitter functions, many neuroamines have trophic or ontogenetic regulatory effects important to both normal and disordered brain development. In previous work (Mejia et al., 2002), we showed that pharmacologically inhibiting monoamine oxidase (MAO) activity during murine gestation increases the prevalence of behaviors thought to reflect impulsivity and aggression. The goal of the present study was to determine the extent to which this treatment influences dopamine and serotonin innervation of murine cortical and subcortical areas, as measured by regional density of dopamine (DAT) and serotonin transporters (SERT). We measured DAT and SERT densities at 3 developmental times (PND 14, 35 and 90) following inhibition of MAO A, or MAO B or both throughout murine gestation and early post-natal development. DAT binding was unaltered within the nigrostriatal pathway, but concurrent inhibition of MAO-A and MAO-B significantly and specifically reduced SERT binding by 10⁻25% in both the frontal cortex and raphe nuclei. Low levels of SERT binding persisted (PND 35, 90) after the termination (PND 21) of exposure to MAO inhibitors and was most marked in brain structures germane to the previously described behavioral changes. The relatively modest level of enzyme inhibition (25⁻40%) required to produce these effects mandates care in the use of any compound which might inhibit MAO activity during gestation.

Expression and localization of CB1R, NAPE-PLD, and FAAH in the vervet monkey nucleus accumbens.

Extensive rodent literature suggests that the endocannabinoid (eCB) system present in the nucleus accumbens (NAc) modulates dopamine (DA) release in this area. However, expression patterns of the cannabinoid receptor type 1 (CB1R), the synthesizing enzyme N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD), and the degradation enzyme fatty acid amide hydrolase (FAAH) in the NAc have not yet been described in non-human primates. The goal of this study is therefore to characterize the expression and localization of the eCB system within the NAc of vervet monkeys (Chlorocebus sabaeus) using Western blots and immunohistochemistry. Results show that CB1R, NAPE-PLD, and FAAH are expressed across the NAc rostrocaudal axis, both in the core and shell. CB1R, NAPE-PLD, and FAAH are localized in medium spiny neurons (MSNs) and fast-spiking GABAergic interneurons (FSIs). Dopaminergic projections and astrocytes did not express CB1R, NAPE-PLD, or FAAH. These data show that the eCB system is present in the vervet monkey NAc and supports its role in the primate brain reward circuit.

Age-related epigenetic changes in hippocampal subregions of four animal models of Alzheimer's disease.

Both aging and Alzheimer's disease (AD) are associated with widespread epigenetic changes, with most evidence suggesting global hypomethylation in AD. It is, however, unclear how these age-related epigenetic changes are linked to molecular aberrations as expressed in animal models of AD. Here, we investigated age-related changes of epigenetic markers of DNA methylation and hydroxymethylation in a range of animal models of AD, and their correlations with amyloid plaque load. Three transgenic mouse models, including the J20, APP/PS1dE9 and 3xTg-AD models, as well as Caribbean vervets (a non-transgenic non-human primate model of AD) were investigated. In the J20 mouse model, an age-related decrease in DNA methylation was found in the dentate gyrus (DG) and a decrease in the ratio between DNA methylation and hydroxymethylation was found in the DG and cornu ammonis (CA) 3. In the 3xTg-AD mice, an age-related increase in DNA methylation was found in the DG and CA1-2. No significant age-related alterations were found in the APP/PS1dE9 mice and non-human primate model. In the J20 model, hippocampal plaque load showed a significant negative correlation with DNA methylation in the DG, and with the ratio a negative correlation in the DG and CA3. For the APP/PS1dE9 model a negative correlation between the ratio and plaque load was observed in the CA3, as well as a negative correlation between DNA methyltransferase 3A (DNMT3A) levels and plaque load in the DG and CA3. Thus, only the J20 model showed an age-related reduction in global DNA methylation, while DNA hypermethylation was observed in the 3xTg-AD model. Given these differences between animal models, future studies are needed to further elucidate the contribution of different AD-related genetic variation to age-related epigenetic changes.

Effects of Prenatal Alcohol Exposure on the Visual System of Monkeys Measured at Different Stages of Development.

Purpose: Fetal alcohol spectrum disorder (FASD) is a developmental disease characterized by behavioral problems and physical defects including malformations of the eye and associated optical defects. How these malformations affect retinal functioning is not well known, although animal models have suggested that scotopic vision is particularly deficient. Age is also known to affect scotopic vision. Here, we determined the combined effects of age and fetal alcohol exposure (FAE) on retinal function using full-field electroretinograms (ERGs) in monkeys (Chlorocebus sabaeus). Methods: ERGs were recorded in monkeys aged 3- to 12-years old, at multiple flash intensities under scotopic and photopic conditions, and functions were fit to the amplitudes of the a- and b-waves. Results: We found that both age and alcohol exposure affected ERGs. In photopic ERGs, amplitudes increased with age, and were higher in FAEs than controls, for data related to the OFF- and ON-pathways. In scotopic ERGs, amplitudes were decreased in young FAE compared with age-matched controls but only for the rod-dominated responses, while at brighter flashes, alcohol exposure led to an increase in the amplitude of the a- and b-waves. Conclusions: The ERGs from the FAE animals closely resembled the data from the older sucrose-control monkeys. This suggests that the FAE monkey retina ages more quickly than the control monkeys. This large sample of nonhuman primates, with carefully monitored ethanol exposure, demonstrates the critical interplay between age and alcohol when assessing the integrity of the retina. We suggest that ERGs might be an important adjunct to diagnosing human FASD.

High Leptospira seroprevalence in captive and wild-caught vervet monkeys ( Chlorocebus sabeus) on the Caribbean island of Saint Kitts.

Leptospirosis is a zoonotic disease of global importance. Very little information is available on Leptospira infection in nonhuman primates. We report herein a high seroprevalence (49.4%; 95% confidence interval: 41.6-57.2%) to Leptospira serovars in vervet monkeys ( Chlorocebus sabeus) on the Caribbean island of Saint Kitts. Monkeys bred in captivity ( n = 81) had a significantly higher seroprevalence compared to wild-caught monkeys ( n = 81; p < 0.05). Seroprevalence to serovar Bataviae was significantly higher in monkeys bred in captivity and was higher to serovar Bratislava in wild-caught monkeys ( p < 0.05). Our data confirm that exposure to various Leptospira serovars and seroconversion occurs in wild and captive vervet monkeys on the Caribbean island of Saint Kitts. Further studies are warranted to better understand epidemiology, transmission, pathology, and possible reservoir status in this species.

Hematologic and biochemical RIs for an aged population of captive African Green monkeys (Chlorocebus aethiops sabaeus).

BACKGROUND: Established RIs for geriatric African Green monkeys (Chlorocebus aethiops sabaeus) are critical for clinical differentiation of normal aging from disease-related changes in this population. OBJECTIVE: The aim of this study was to establish hematologic and serum biochemical RIs for a Caribbean captive population of geriatric (≥ 15 years of age) African Green monkeys, or Vervets. METHODS: Inclusion and exclusion criteria were defined for a cohort of 109 healthy, aged (15- to 30-year-old, median 19-year-old) Vervets. Both male (34) and female (75) monkeys were included in RI generation. Complete manual and analyzer-generated blood counts and serum biochemistry profiles were performed at Ross University School of Veterinary Medicine, West Farm, St. Kitts, West Indies. All results were evaluated using Reference Value Advisor. Isolated outliers were identified using Dixon's outlier range statistic and not included in determination of RIs for individual analytes. Reference intervals were determined using parametric and nonparametric methods depending on the distribution. Data, including mean, median, maximum, and minimum values, were tabulated. RESULTS: Of the 109 animals, 12 monkeys were excluded due to abnormal physical examination results (2 monkeys), and ≥ 2 confirmed outliers (9 monkeys), or evidence of disease based on laboratory data (one monkey). CONCLUSIONS: This study provides useful RIs for assessment of hematology and serum biochemical variables in a geriatric population of African Green monkeys in the Caribbean.