Early lead exposure effects on an auditory threshold task in the rhesus monkey (Macaca mulatta)

Behavioral thresholds to pure tones were obtained from adult rhesus monkeys that had been exposed to lead during early development and unexposed cohort controls. Thresholds were elevated (by 2–9 dB) for the previously lead exposed monkeys at all frequencies tested (125–8,000 Hz in octave steps). Although the magnitude and direction of the differences were similar to significant effects reported for children, the more difficult task and much smaller sample sizes in this study of monkeys may have precluded obtaining significant differences at the same magnitude of effects observed in children. Thresholds for one lead‐exposed monkey were significantly elevated at midrange frequencies in agreement with electrophysiological results obtained in another study [Lasky, Maier, Snodgrass, Hecox, and Laughlin [1995] Neurotoxicology and Teratology, 17, 633–644]. Behavioral measurements during the threshold task indicated less engagement for lead exposed monkeys than for controls. In addition, the lead exposed monkeys completed testing at significantly fewer frequencies and were significantly more difficult to test than control monkeys by tester ratings. These results are consistent with reports concerning the behavior of lead exposed children. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 289–300, 2009     

Permeability characteristics and osmotic sensitivity of rhesus monkey (Macaca mulatta) oocytes

BACKGROUND: Permeability characteristics and sensitivity to osmotic shock are principal parameters that are important to derive procedures for the successful cryopreservation of mammalian oocytes. METHODS AND RESULTS: The osmotically inactive volume of rhesus monkey oocytes was determined by measuring their volumes in the presence of hypertonic solutions of sucrose from 0.2 to 1.5 mol/l, compared with their volume in isotonic TALP-HEPES solution. Boyle-van't Hoff plots at infinite osmolality indicated that the non-osmotic volumes of immature and mature oocytes were 20 and 17% respectively. Osmotic responses of oocytes exposed to 1.0 mol/l solutions of glycerol, dimethylsulphoxide (DMSO) and ethylene glycol (EG) were determined. Rhesus monkey oocytes appeared to be less permeable to glycerol than to DMSO or to EG. Sensitivity of oocytes to osmotic shock was determined by exposing them to various solutions of EG (0.1 to 5.0 mol/l) and then abruptly diluting them into isotonic medium. Morphological survival, as measured by membrane integrity, of oocytes diluted out of EG depended significantly on the concentration of EG (P < 0.01). CONCLUSION: Determination of permeability characteristics and sensitivity to osmotic shock of rhesus oocytes will aid in the derivation of procedures for their cryopreservation.     

Adiposity and weight gain during pregnancy associate independently with behavior of infant rhesus monkeys (Macaca mulatta)

Growing evidence identifies maternal adiposity as a potentially modifiable risk factor for adverse neurodevelopment. This retrospective cohort analysis examined whether maternal prepregnancy adiposity and gestational weight gain were associated with behavioral outcomes in 173 rhesus macaque infants at the California National Primate Research Center. Dams conceived indoors, had uncomplicated pregnancies, delivered vaginally, and reared infants indoors. Infants underwent standardized biobehavioral analysis at 90–120 days of age from 3/2001–5/2015. Offspring of mothers with greater baseline adiposity or gestational weight gain exhibited a pattern of poor adaptability characterized by greater emotionality as the assessments proceeded, blunted affective response to a human intruder challenge, and reduced interest in novel stimuli which is associated with poorer social functioning later in life. They also had lower cortisol levels following dexamethasone suppression, perhaps a response to cortisol excess during gestation. These results amplify growing public health concerns implicating maternal adiposity in impaired fetal neurobehavioral programming.     

Postnatal lead effects on the development of visual spatial acuity in rhesus monkeys (Macaca Mulatta)

High lead levels adversely affect visual function in humans and laboratory animals. The effects of lower lead levels are less certain. This study compared the development of photopic spatial acuity in rhesus monkeys exposed to lead (n = 43) with monkeys (n = 23) not exposed to lead. Lead exposure began at Day 8 postpartum and continued daily throughout the first 26 weeks of postnatal life achieving target blood lead levels of 35-40 microg/dl by about 15 weeks. Photopic spatial acuity was evaluated by a preferential looking technique used clinically to assess spatial acuity in human infants. Acuity increased rapidly over the first few postnatal weeks achieving the maximum acuity level assessed (26.3 c/deg) by 7 weeks of age for most monkeys. Postnatal lead exposure at the dosages and durations studied did not affect the development of photopic spatial acuity.     

Clinical applications of auditory event related potentials in neurology

Summary Auditory ERP (AERP) studies have been performed in 56 patients with central nervous system disturbances. Forty seven patients(90.5%), had AERP component abnormalities concerning mainly P300 topography alterations and secondarily P300 latency prolongation. It is concluded that P300 is a very useful tool in clinical neurology and that P300 topography or latency alterations are not specific of any cerebral disturbance but can be found in any disease whenever cognitive functions are impaired.     

Head orientation and handedness trajectory in rhesus monkey infants (Macaca mulatta)

In human and chimpanzee infants, neonatal rightward supine head orientation bias predicts later right hand use preference. In an evolutionarily older primate species such as the rhesus monkey, a left hand preference has been reported, but there are no data on head orientation biases. Supine head orientation bias was measured experimentally in 16 rhesus monkey neonates and compared with prone head orientation bias as well as with various measures of hand use preference. A group-level leftward supine head bias was found that corresponded to greater activity in the left hand while supine; however, supine head orientation did not predict later hand preference as measured by reaching or manipulation on a coordinated bimanual task. These data suggest that a trajectory for handedness in rhesus monkeys may be different from that of humans and chimpanzees.     

Experimental Helicobacter pylori infection of rhesus macaques (Macaca mulatta)

The aim of the present study was to establish an animal model for Helicobacter pylori (H. pylori) infection at the German Primate Centre in rhesus monkeys (Macaca mulatta). During the experiments the susceptibility of three animals to different H. pylori strains of human origin was tested. In a follow-up study gastric biopsies from three different sites were investigated in regular intervals using microbiological, histological, electron microscopical and molecular biological methods to evaluate the presence of bacterial colonization and the occurrence of gastritis. It was possible to establish a persistent experimental infection. The rather long follow-up period of 18 months offered the possibility to demonstrate a permanent H. pylori infection in the gastric mucosa of the test animals. The three animals have now been successfully colonized with H. pylori for 18 months and presented a chronic active gastritis confirmed by microbiological and histological methods. By molecular typing, the identity of the isolates recovered from the animals was shown. It was possible to demonstrate that one infection strain outcompeted the second one. Taken together, prerequisites exist for making use of an attractive and useful animal model in rhesus monkeys especially for long term observations.     

Changes in structure and functions of prostate by long-term administration of an androgen,testosterone enanthate,in rhesus monkey (Macaca mulatta)

The increasing use of androgens in clinical trials for developing a safe, effective, and reversible male contraceptive has necessitated a critical evaluation of the effects of their long-term use on the structure and functions of the prostate gland, which is androgen dependent. Combination regimens using progestogens, gonadotropin-releasing hormone antagonists, or antiandrogens along with androgens are undergoing clinical evaluation as antispermatogenic agents. The majority of these regimens have used testosterone enanthate (TE) as the androgen of choice, but very limited information is available on the side effects of long-term androgen use. The present study is the first report that critically evaluates the effects of long-term use of TE on prostate structure and functions. Adult male rhesus monkeys received intramuscular injections of 50 mg of TE once in 14 days for 33 months. The cranial and caudal lobes of the prostate, which were removed under ketamine anesthesia, were processed for the preparation of semithin sections to evaluate histological changes. The DNA distribution in the cells was studied in single cell suspensions of cranial and caudal lobes of the prostate by using flow cytometry. Changes in the levels of testosterone, estradiol, prostate-specific acid phosphatase (PAP), and prostate-specific antigen (PSA) in samples collected during the pretreatment period and at the time of removal of the prostate were estimated by using conventional procedures. Control samples were processed simultaneously. The administration of TE for 33 months caused the following changes: 1) significant increase in the weight of both lobes of the prostate, 2) cellular hypertrophy and increase in secretory material in the cells and in the lumen of the acini in the central and peripheral zones of the two lobes of the prostate, 3) cellular hyperplasia indicated by flow cytometric analysis of DNA content, 4) significant increase in the secretion of PAP and levels of estradiol, and 5) a marked increase in fibromuscular stroma in the central and peripheral zones of both the lobes of the prostate. The present study is the first report to provide evidence that long-term androgen treatment has caused hypertrophy of the prostatic epithelial cells, which showed increased secretory activity. The hyperplastic changes indicate a need for the development of new androgens with a better pharmacokinetic profile for use in male contraceptive regimens. Anat. Rec. 252:637–645, 1998. © 1998 Wiley-Liss, Inc.     

Surrogate mobility and orientation affect the early neurobehavioral development of infant rhesus macaques (Macaca mulatta)

A biological mother's movement appears necessary for optimal development in infant monkeys. However, nursery‐reared monkeys are typically provided with inanimate surrogate mothers that move very little. The purpose of this study was to evaluate the effects of a novel, highly mobile surrogate mother on motor development, exploration, and reactions to novelty. Six infant rhesus macaques (Macaca mulatta) were reared on mobile hanging surrogates (MS) and compared to six infants reared on standard stationary rocking surrogates (RS) and to 9–15 infants reared with their biological mothers (MR) for early developmental outcome. We predicted that MS infants would develop more similarly to MR infants than RS infants. In neonatal assessments conducted at Day 30, both MS and MR infants showed more highly developed motor activity than RS infants on measures of grasping (p = .009), coordination (p = .038), spontaneous crawl (p = .009), and balance (p = .003). At 2–3 months of age, both MS and MR infants displayed higher levels of exploration in the home cage than RS infants (p = .016). In a novel situation in which only MS and RS infants were tested, MS infants spent less time near their surrogates in the first five minutes of the test session than RS infants (p = .05), indicating a higher level of comfort. Collectively, these results suggest that when nursery‐rearing of infant monkeys is necessary, a mobile hanging surrogate may encourage more normative development of gross motor skills and exploratory behavior and may serve as a useful alternative to stationary or rocking surrogates. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 418–422, 2008.     

Rearing environment and hypothalamic-pituitary-adrenal regulation in young rhesus monkeys (Macaca mulatta)

A mammal's early social environment has important regulatory effects on its behavior and physiology, and this is especially true for regulation of the hypothalamic-pituitary-adrenal (HPA) system. The present study was designed to test hypotheses that various aspects of the social environment are important influences on HPA regulation. Seven hundred seventy eight, 3- to 4-month-old rhesus monkeys were studied as part of a standardized, 24-hr biobehavioral assessment program, which included blood sampling to determine plasma cortisol concentrations. Results indicate that nursery-rearing results in a reduced cortisol set-point for the HPA system, and, for nursery-reared (NR) animals, more peer exposure during infancy is associated with a higher set-point. Age and sex differences during this period were evident but small in magnitude. These data demonstrate the important regulatory role of the social environment on nonhuman primate physiology and suggest caution in assuming that differences between individuals' cortisol levels reflect only differences in perceptions of the "stressfulness" of events.     

Ovarian senescence in the rhesus monkey (Macaca mulatta)

BACKGROUND: A decline in fertility is evident in human females past their middle thirties. This 'reproductive senescence', marked by a sharp decline in pregnancy rates, may be attributed to reductions in numbers of available oocytes and their quality. Because Old World primates exhibit ovarian morphology and physiological control and timing of menstrual cycles closely resembling those of humans, the current study investigated the rhesus macaque as a potential model for human reproductive senescence. METHODS: Ovaries collected from females aged 1-25 years and divided into five age groups were analysed histologically. RESULTS: General ovarian morphology demonstrated significant changes as the females approached menopause. The proportions of primordial and primary follicles all demonstrated significant differences across age groups (primordial: 77.1, 79.9, 69.7, 62.9, 55.1%; primary: 21.5, 18.8, 28.5, 35.2, 43.1% for age groups 1 to 5 respectively; P<0.0001 for both). Samples from females approaching or undergoing the menopausal transition (aged 20-25 years) demonstrated evidence of ovarian senescence, having scattered and atretic follicles, low numbers of primordial follicles and reduced stromal tissue. CONCLUSION: This study supports the value of the rhesus monkey as a model for reproductive ageing because its ovary undergoes follicular reservoir depletion similar to that seen in humans.     

Long-term effects of infant rearing condition on the acquisition of dominance rank in juvenile and adult rhesus macaques (Macaca mulatta)

We examined the effects of early rearing experience on the development of dominance status in 53 juvenile (age 3) and then in 38 adult (ages 5-8) rhesus macaques. Based on previous research investigating the behavioral outcomes of nursery-rearing, we predicted that mother-reared (MR) monkeys would outrank peer-only reared (PR) monkeys, which would in turn outrank surrogate/peer-reared (SPR) subjects. Juvenile MR and PR subjects did not differ in ranks, but monkeys from both rearing backgrounds outranked SPR cage-mates at age 3. Independent of rearing condition, high-ranking juveniles gained the most weight between ages 1-3, suggesting that low status may be associated with decreases in early weight gain. Adult MR subjects outranked both PR and SPR subjects, with PR animals occupying intermediate ranks. These results indicate that impoverished early experiences, such as adult absence and limited social interaction, are useful predictors of future social success in rhesus macaques.     

Alzheimer's Abeta vaccination of rhesus monkeys (Macaca mulatta)

Recent preliminary data suggest that vaccination with Alzheimer's Abeta might reduce senile plaque load and stabilize cognitive decline in human Alzheimer's disease. To examine the mechanisms and consequences of anti-Abeta-antibody formation in a species more closely related to humans, rhesus monkeys (Macaca mulatta) were vaccinated with aggregated Abeta(1-42). Immunized monkeys developed anti-Abeta titers exceeding 1:1000, and their plasma Abeta levels were 5-10-fold higher than the plasma Abeta levels observed in monkeys vaccinated with aggregated amylin. These data support the use of non-human primates to model certain phenomena associated with vaccination of humans with aggregated Alzheimer's Abeta.     

Ontogeny of hallucal metatarsal rigidity and shape in the rhesus monkey (Macaca mulatta) and chimpanzee (Pan troglodytes)

Life history variables including the timing of locomotor independence, along with changes in preferred locomotor behaviors and substrate use during development, influence how primates use their feet throughout ontogeny. Changes in foot function during development, in particular the nature of how the hallux is used in grasping, can lead to different structural changes in foot bones. To test this hypothesis, metatarsal midshaft rigidity [estimated from the polar second moment of area (J) scaled to bone length] and cross‐sectional shape (calculated from the ratio of maximum and minimum second moments of area, I_max/I_min) were examined in a cross‐sectional ontogenetic sample of rhesus macaques (Macaca mulatta; n = 73) and common chimpanzees (Pan troglodytes; n = 79). Results show the hallucal metatarsal (Mt1) is relatively more rigid (with higher scaled J‐values) in younger chimpanzees and macaques, with significant decreases in relative rigidity in both taxa until the age of achieving locomotor independence. Within each age group, Mt1 rigidity is always significantly higher in chimpanzees than macaques. When compared with the lateral metatarsals (Mt2–5), the Mt1 is relatively more rigid in both taxa and across all ages; however, this difference is significantly greater in chimpanzees. Length and J scale with negative allometry in all metatarsals and in both species (except the Mt2 of chimpanzees, which scales with positive allometry). Only in macaques does Mt1 midshaft shape significantly change across ontogeny, with older individuals having more elliptical cross‐sections. Different patterns of development in metatarsal diaphyseal rigidity and shape likely reflect the different ways in which the foot, and in particular the hallux, functions across ontogeny in apes and monkeys.     

Cerebellar regulation of phonation in rhesus monkey (Macaca mulatta)

Summary Five rhesus monkeys (Macaca mulatta) were trained to emit a coo vocalization with a duration of at least 500 msec. After stable performance was achieved cerebellar lesions were introduced, and various pre- and postlesion measures of phonation and of laryngeal EMG activity were compared to assess the effects of the lesions. The phonatory changes were interpreted with respect to possible laryngeal or respiratory modifications. The relation between fundamental frequency and intensity of phonation was changed in some animals, with no obvious alterations in either fundamental frequency or intensity considered separately. Intensity of phonation was decreased while duration was prolonged in two animals. Fundamental frequency of phonation was also affected in some animals. Reliable laryngeal EMG was obtained in two animals and was affected by cerebellar lesions. These results indicate that normal cerebellar function is involved in the control of fundamental frequency, intensity, duration, and the coordination of the laryngeal and respiratory systems for the control of phonation.