Behavioral effects of low,acute doses of d-amphetamine on the dyadic interaction between mother and infant vervet monkeys (Cercopithecus aethiops) during the first six postnatal months

Doses of d-amphetamine sulfate (0.1, 0.15, and 0.2 mg/kg body weight) were given to adult monkeys in mother—infant pairs. The fundamental parental care behavior pattern was disrupted and the mother became isolated in a socially withdrawn phase. She did not respond to the calling signals of the infant and showed behavior in which stereotyped self-grooming and/or staring into space were predominant. The reactions of the infant to this amphetamine-induced behavior were different in the two experimental pairs. In group 1 the infant increased its approach—avoidance movements. In group 2 the infant sat very quietly and close in front of the mother. The mother from group 1 reacted to the increased approaches from its ininfant with active rejection. In both groups the mothers did not react with the typical ventral—ventral grasping to either the infants sitting close or to the social anxiety signals of the infants. In spite of differences in behavior changes induced by amphetamine, the main conclusion is that the mothers totally lost their normal and highly biologic significant interest in their infants.     

The presence of α-glucosidase, glycerophosphocholine and carnitine in the epididymis and ejaculate of the vervet monkey (Cercopithecus aethiops) and the Chacma baboon (Papio ursinus)

Summary.  The epididymis is the site of post-testicular sperm maturation in the male genital tract. Studies on human epididymides are hampered by the practical inaccessibility of epididymides of healthy men in their reproductive years. The limited use of laboratory animals therefore seems unavoidable. The objective was to establish baseline values of the epididymal markers α-glucosidase, glycerophosphocholine (GPC) and carnitine in the lumen of the caput, corpus and cauda epididymidis and in the ejaculate of adult male Chacma baboons and vervet monkeys. In both primates, α-glucosidase was found throughout the epididymis and in the ejaculate; values did not vary significantly. In monkeys, the highest concentration of GPC was found in the cauda epididymidis, but smaller amounts were found in the other regions and the ejaculate. In baboons, GPC was absent from the caput, but present in the other regions, including the ejaculate. Carnitine concentrations increased significantly from the caput to the cauda in monkeys and from the caput to the corpus in baboons. With this study, the relative concentration ranges in which these markers are present in the epididymides of these primates have been established. In future studies, changes in concentrations of these substances would probably indicate changes in epididymal function.     

Developmental patterns of hair cortisol in male and female nonhuman primates: Lower hair cortisol levels in vervet males emerge at puberty

Studies have yielded inconsistent results with regard to effects of age and sex on short-term markers of hypothalamic pituitary adrenal (HPA) activity. Hair cortisol provides a retrospective proxy measure of the cumulative activity of the HPA axis over the preceding 3- to 4-month period. In order to describe potential developmental trends in this biomarker, we assessed hair cortisol levels between 1 and 12 years of age in a cross-sectional study of 350 vervets (222 females and 128 males). Monkeys were grouped according to age as 1 (young juvenile), 2 (juvenile), 3 (early adolescent), 4 (late adolescent-young adult), and 5-12 (adult) years of age such that fully mature animals were included in the 5-12 year old age group. We observed that hair cortisol level was higher among the younger monkeys and declined with age (p<.001). More importantly the effect of age significantly interacted with sex (p=.02), such that hair cortisol was consistently lower in males than females beginning at age 3 (p<.05 or better). The developmental decline began one year earlier in females than males suggesting an influence of the earlier maturational processes typical in both human and nonhuman primates. The advantage of lower cortisol levels in the males may be related to social group patterns of male emigration during adolescence in many nonhuman primate species.     

Dopaminergic innervation of the pallidum in the normal state, in MPTP-treated monkeys and in parkinsonian patients

The aim of the present study was to characterize the dopaminergic innervation of the pallidum in primates (humans and Cercopithecus aethiops). Firstly, in monkeys, biotin dextran amine was injected into dopaminergic areas, and the anterogradely labelled axons were reconstructed from serial sections and analysed in the pallidum. Secondly, in parkinsonian patients and MPTP-treated monkeys, the dopaminergic innervation of the pallidum was studied using tyrosine hydroxylase-positive fibre quantification. Our study revealed that dopaminergic areas A8 and A9 innervated the two pallidal segments. Individual axonal arborizations displayed a great heterogeneity. Some dopaminergic axons crossed the pallidum without branching, other axons made small terminal arborizations in a restricted region of one pallidal segment, whereas others developed dense arborizations covering extended areas in the two pallidal segments. This heterogeneous organization suggests that dopamine could directly modulate the pallidum using either a point-to-point or a diffuse projection pattern. A statistically significant loss of dopaminergic fibres in the internal (-43%) and external pallidum (-39.6%) of humans, and in the internal (-54.3%) and external pallidum (-59%) of monkeys was revealed in parkinsonian states. The consequences of this alteration are still unknown but it might participate in the triggering of motor symptoms observed in Parkinson's disease.     

An amino acid mixture deficient in phenylalanine and tyrosine reduces cerebrospinal fluid catecholamine metabolites and alcohol consumption in vervet monkeys

 An amino acid mixture devoid of tryptophan, given orally, was previously shown to reduce cerebrospinal fluid levels of tryptophan and 5-hydroxyindoleacetic acid in vervet monkeys, as compared to a control mixture containing all essential amino acids. In the present study, we tested the possibility that a similar amino acid mixture containing tryptophan, but devoid of phenylalanine and tyrosine (the amino acid precursors of catecholamine neurotransmitters), would influence dopamine and noradrenaline metabolism. Five hours after the administration of this mixture to vervet monkeys, cerebrospinal fluid levels of homovanillic acid and 3-methoxy-4-hydroxyphenylethylene glycol were reduced by 27.4% and 26.9%, respectively. Both effects were statistically significant. Plasma tyrosine (-30%) and the ratio of tyrosine to the sum of other large neutral amino acids (ΣLNAA) were also significantly reduced. The behavioral efficacy of phenylalanine/tyrosine depletion was compared with that of tryptophan depletion in a primate model of voluntary alcohol consumption. All three drinks lowered alcohol consumption, but the effects of the tryptophan-deficient amino acid mixture were not different from those of the balanced amino acid control. The phenylalanine/tyrosine-deficient drink differentially lowered alcohol consumption, consistent with other data in this species and elsewhere implicating dopamine in the rewarding effects of alcohol. Received: 14 January 1997 / Final version: 10 September 1997     

Intra-Host SARS-CoV-2 Evolution in the Gut of Mucosally-Infected Chlorocebus aethiops (African Green Monkeys)

In recent months, several SARS-CoV-2 variants have emerged that enhance transmissibility and escape host humoral immunity. Hence, the tracking of viral evolutionary trajectories is clearly of great importance. Little is known about SARS-CoV-2 evolution in nonhuman primate models used to test vaccines and therapies and to model human disease. Viral RNA was sequenced from rectal swabs from Chlorocebus aethiops (African green monkeys) after experimental respiratory SARS-CoV-2 infection. Two distinct patterns of viral evolution were identified that were shared between all collected samples. First, mutations in the furin cleavage site that were initially present in the virus as a consequence of VeroE6 cell culture adaptation were not detected in viral RNA recovered in rectal swabs, confirming the necessity of this motif for viral infection in vivo. Three amino acid changes were also identified; ORF 1a S2103F, and spike D215G and H655Y, which were detected in rectal swabs from all sampled animals. These findings are demonstrative of intra-host SARS-CoV-2 evolution and may identify a host-adapted variant of SARS-CoV-2 that would be useful in future primate models involving SARS-CoV-2 infection.     

转瓶培养非洲绿猴肾传代细胞生产纯化流行性乙型脑炎疫苗的研究

目的研究用１５Ｌ转瓶培养非洲绿猴肾传代细胞（Ｖｅｒｏ细胞）生产纯化流行性乙型脑炎（以下简称乙脑）疫苗的工艺,提高乙脑疫苗的质量。方法用１５Ｌ转瓶培养Ｖｅｒｏ细胞和扩增乙脑病毒,病毒经过灭活、浓缩、硫酸鱼精蛋白处理、蔗糖密度梯度区带离心纯化,制备成冻干疫苗。结果建立了一套１５Ｌ转瓶培养Ｖｅｒｏ细胞生产纯化乙脑疫苗的工艺,用此工艺制备三批冻干疫苗,经检定疫苗质量达到同类产品的国际水平,已通过新药审评,人体安全性和效果观察正在进行中。结论转瓶培养Ｖｅｒｏ细胞生产纯化乙脑疫苗是可行的。     

A novelty seeking phenotype is related to chronic hypothalamic-pituitary-adrenal activity reflected by hair cortisol

Reduced hypothalamic pituitary adrenal (HPA) activity is associated with greater novelty seeking in humans. Hair cortisol represents an integrated proxy measure of total cortisol production/release over an extended period of time and may be a valuable tool for tracking the HPA system. Sampling approaches (collection of blood, saliva, urine, or feces) for socially housed nonhuman primates present a number of technical challenges for collection particularly when repeated sampling is necessary. Herein we describe a relationship between cortisol levels measured in hair collected from 230 socially housed female vervet (Chlorocebus aethiops sabaeus) monkeys and a free-choice novelty seeking phenotype. A predator-like object was placed at the periphery of the outdoor enclosures for 30 min and speed of approach (latency to approach within 1 m) and persistence of interest (number of 1 min intervals within 1 m) were scored. A composite Novelty Seeking score, combining these two measures, was calculated. The intra-class correlation coefficient (ICC = .68) for two different objects across years indicated that this score reflects a stable aspect of temperament. Hair samples were collected from each subject approximately 3-6 months following the second assessment; cortisol levels were determined from the hair. A significant inverse relationship of Novelty Seeking score with hair cortisol level (p < .01) was noted. The high hair cortisol groups had significantly lower Novelty Seeking scores than the low cortisol groups both years (p's < .05). These results suggest that low average cortisol levels promote novelty seeking, while high average levels inhibit novelty seeking behavior.     

Retention of leptospiral agglutinins and long-term response to administration of monoclonal antibodies in vervet monkeys (Cercopithecus aethiops) on Barbados

In a study of 21 wild-caught Barbadian vervet monkeys (Cercopithecus aethiops sabaeus), naturally-acquired- leptospiral agglutinins were found to persist for over five years. Groups of seropositive as well as seronegative vervets were given a placebo, or full-strength monoclonal antibodies MCA F12C3 (Icterohaemorrhagiae copenhageni), or diluted F12C3 MCAs. They were challenged 24 hours later with a suspension of highly virulent leptospires (copenhageni) administered intraperitoneally.Immunoprotection was evident in animals receiving full strength MCAs as measured by their failure to develop any substantial antibody response and by their lower geometric mean titres over a period of 142 weeks (maximum GMT of 113 compared with a maximum of 1280 in the placebo group). Diluted MCAs had little or no protective value. The serological response of the monkeys which were seropositive at capture to challenge with virulent copenhageni antigen was strongly anamnestic both in those given MCAs and those given placebo. None of the naturally or experimentally infected vervets showed clinical signs of leptospiral illness.Corresponding author.     

氯仿对非洲绿猴肾细胞损伤机理的研究

目的　实验研究氯仿染毒 2 4h对非洲绿猴肾细胞的损伤及其机理。方法　运用显微荧光术测定了非洲绿猴肾细胞 (Vero细胞 )内活性氧 (ROS)含量及游离Ca2 + 浓度 ,同时 ,测定Vero细胞培养上清液乳酸脱氢酶(LDH)活力用于检查Vero细胞受损情况。结果　接触浓度为 4 0mmol L氯仿的Vero细胞内ROS含量及游离Ca2 +浓度与对照组比较无显著性差异 (P >0 0 5 ) ,同时 ,表示Vero细胞受损指标 (LDH活力 )也无显著性差异 (P >0 0 5 ) ;而接触浓度为 8 0mmol L、12 0mmol L氯仿的Vero细胞内ROS含量显著高于对照组 (P <0 0 1) ,其Vero细胞受损也显著增加 (P <0 0 5、P <0 0 1)。结论　较高浓度的氯仿能损伤Vero细胞 ,其损伤的可能途径是通过提高Vero细胞内ROS含量