Interventional ultrasound in pregnant macaques: embryonic/fetal applications

Similarities in developmental biology between human and nonhuman primates have resulted in the use of macaque species as models in perinatal research. Studies have frequently included invasive surgical procedures or may have required "blind" injections. Several techniques have been established in human subjects using ultrasound as a guide such as cordocentesis and fetal therapy. These techniques have been applied to the nonhuman primate laboratory setting, which significantly decreases the risk of pregnancy loss due to experimental intervention.     

Stereotypies in Captive Primates and the Use of Inositol: Lessons from Obsessive–Compulsive Disorder in Humans

Animal stereotypies have long been used in the study of obsessive–compulsive disorder (OCD) in humans. These studies have led to the understanding of some of the molecular pathways in the disorder and the use of selective serotonin reuptake inhibitors and myo-inositol in the treatment of these conditions. If animal models, especially nonhuman primate models, were used to study human disorders and if the resulting treatments were successful, then conversely one should be able to treat nonhuman primate stereotypies with similar methods. We here summarize animal models of OCD (including nonhuman primate models) and human OCD treatments, and using successful human treatment by myo-inositol as models, recommend the use of myo-inositol in good captive management practice and the treatment of nonhuman primate stereotypies. We believe that this would be particularly useful in the treatment of stereotypies in nonhuman primates because they are physiologically so similar to humans.     

Eye-tracking with nonhuman primates is now more accessible than ever before

Human and nonhuman primates rely almost exclusively on vision for social communication. Therefore, tracking eye movements and examining visual scan paths can provide a wealth of information about many aspects of primate social information processing. Although eye-tracking techniques have been utilized with humans for some time, similar studies in nonhuman primates have been less frequent over recent decades. This has largely been owing to the need for invasive manipulations, such as the surgical implantation of devices to limit head movement, which may not be possible in some laboratories or at some universities, or may not be congruent with some experimental aims (i.e., longitudinal studies). It is important for all nonhuman primate researchers interested in visual information processing or operant behavior to realize that such invasive procedures are no longer necessary. Here, we briefly describe new methods for fully noninvasive video eye-tracking with adult rhesus monkeys (Macaca mulatta). We also describe training protocols that require only ～30 days to accomplish and quality control measures that promote reliable data collection. It is our hope that this brief overview will reacquaint nonhuman primate researchers with the benefits of eye-tracking and promote expanded use of this powerful methodology.     

Nonhuman primate infections after organ transplantation

Nonhuman primates, primarily rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis), and baboons (Papio spp.), have been used extensively in research models of solid organ transplantation, mainly because the nonhuman primate (NHP) immune system closely resembles that of the human. Nonhuman primates are also frequently the model of choice for preclinical testing of new immunosuppressive strategies. But the management of post-transplant nonhuman primates is complex, because it often involves multiple immunosuppressive agents, many of which are new and have unknown effects. Additionally, the resulting immunosuppression carries a risk of infectious complications, which are challenging to diagnose. Last, because of the natural tendency of animals to hide signs of weakness, infectious complications may not be obvious until the animal becomes severely ill. For these reasons the diagnosis of infectious complications is difficult among post-transplant NHPs. Because most nonhuman primate studies in organ transplantation are quite small, there are only a few published reports concerning infections after transplantation in nonhuman primates. Based on our survey of these reports, the incidence of infection in NHP transplant models is 14%. The majority of reports suggest that many of these infections are due to reactivation of viruses endemic to the primate species, such as cytomegalovirus (CMV), polyomavirus, and Epstein-Barr virus (EBV)-related infections. In this review, we address the epidemiology, pathogenesis, role of prophylaxis, clinical presentation, and treatment of infectious complications after solid organ transplantation in nonhuman primates.     

Neurocognitive effects of estrogens across the adult lifespan in nonhuman primates: State of knowledge and new perspectives

This article is part of a Special Issue "Estradiol and cognition".This review discusses the unique contribution of nonhuman primate research to our understanding of the neurocognitive effects of estrogens throughout the adult lifespan in females. Mounting evidence indicates that estrogens affect many aspects of hippocampal, prefrontal and cholinergic function in the primate brain and the underlying mechanisms are beginning to be elucidated. In addition, estrogens may also influence cognitive function indirectly, via the modulation of other systems that impact cognition. We will focus on the effects of estrogens on sleep and emphasize the need for primate models to better understand these complex interactions. Continued research with nonhuman primates is essential for the development of therapies that are optimal for the maintenance of women's cognitive health throughout the lifespan.     

Models of focal cerebral ischemia in the nonhuman primate

Ischemic stroke is a uniquely human disease syndrome. Models of focal cerebral ischemia developed in nonhuman primates provide clinically relevant platforms for investigating pathophysiological alterations associated with ischemic brain injury, microvascular responses, treatment responses, and clinically relevant outcomes that may be appropriate for ischemic stroke patients. A considerable number of advantages attend the use of nonhuman primate models in cerebral vascular research. Appropriate development of such models requires neurosurgical expertise to produce single or multiple vascular occlusions. A number of experimentally and clinically accessible outcomes can be measured, including neurological deficits, neuron injury, evidence of non-neuronal cell injury, infarction volume, real-time imaging of injury development, vascular responses, regional cerebral blood flow, microvascular events, the relation between neuron and vascular events, and behavioral outcomes. Nonhuman primate models of focal cerebral ischemia provide excellent opportunities for understanding the vascular and cellular pathophysiology of cerebral ischemic injury, which resembles human ischemic stroke, and the appropriate study of pharmacological interventions in a human relevant setting.     

非人灵长类糖尿病动物模型研究进展

糖尿病是继心血管疾病和肿瘤之后的另一种严重危害人类健康的重要慢性疾病,据世界卫生组织(WHO)报道,2009年全世界约有2.2亿糖尿病患者。对糖尿病发病机理的研究、预防和诊断、治疗药物的筛选和评价都需要合适的动物模型。在已报道的糖尿病动物模型中,非人灵长类动物糖尿病病程、病症与人类的糖尿病最为相似。该文从糖尿病动物模型的来源归纳了目前报道的主要的非人灵长类糖尿病模型,重点介绍了猕猴、食蟹猴和树鼩糖尿病模型及其特征,并对该领域的发展提出了一些思考。     

Monkey models of recovery of voluntary hand movement after spinal cord and dorsal root injury

The hand is unique to the primate and manual dexterity is at its finest in the human (Napier 1980), so it is not surprising that cervical spinal injuries that even partially block sensorimotor innervation of the hand are frequently debilitating (Anderson 2004). Despite the clinical need to understand the neuronal bases of hand function recovery after spinal and/or nerve injuries, relatively few groups have systematically related subtle changes in voluntary hand use following injury to neuronal mechanisms in the monkey. Human and macaque hand anatomy and function are strikingly similar, which makes the macaque the favored nonhuman primate model for the study of postinjury dexterity. In this review of monkey models of cervical spinal injury that have successfully related voluntary hand use to neuronal responses during the early postinjury months, the focus is on the dorsal rhizotomy (or dorsal rootlet lesion) model developed and used in our laboratory over the last several years. The review also describes macaque monkey models of injuries to the more central cervical spine (e.g., hemisection, dorsal column) that illustrate methods to assess postlesion hand function and that relate it to neurophysiological and neuroanatomical changes. Such models are particularly important for understanding what the sensorimotor pathways are capable of, and for assessing the outcome of therapeutic interventions as they are developed.     

Rodent laparoscopy: refinement for rodent drug studies and model development, and monitoring of neoplastic, inflammatory and metabolic diseases

The refinement of surgical techniques represents a key opportunity to improve the welfare of laboratory rodents, while meeting legal and ethical obligations. Current methods used for monitoring intra-abdominal disease progression in rodents usually involve euthanasia at various time-points for end of study, one-time individual tissue collections. Most rodent organ tumour models are developed by the introduction of tumour cells via laparotomy or via ultrasound-guided indirect visualization. Ischaemic rodent models are often generated using laparotomies. This approach requires a high number of rodents, and in some instances introduces high degrees of morbidity and mortality, thereby increasing study variability and expense. Most importantly, most laparotomies do not promote the highest level of rodent welfare. Recent improvements in laparoscopic equipment and techniques have enabled the adaptation of laparoscopy for rodent procedures. Laparoscopy, which is considered the gold standard for many human abdominal procedures, allows for serial biopsy collections from the same animal, results in decreased pain and tissue trauma as well as quicker postsurgical recovery, and preserves immune function in comparison to the same procedures performed by laparotomy. Laparoscopy improves rodent welfare, decreases inter-animal variability, thereby reducing the number of required animals, allows for the replacement of larger species, decreases expense and improves data yield. This review article compares rodent laparotomy and laparoscopic surgical methods, and describes the utilization of laparoscopy for the development of cancer models and assessment of disease progression to improve data collection and animal welfare. In addition, currently available rodent laparoscopic equipment and instrumentation are presented.     

Role of the nonhuman primate for research related to women's health

This overview of the current status of medical problems that affect women is related to current studies on pathophysiology and therapeutic interventions using nonhuman primates to demonstrate the utility of the primate model for the study of disease processes in women. The current medical literature on women's health is compared with the literature on nonhuman primate research. The findings reviewed in the articles of ILAR Journal Volume 45 Issue 2 of 2004 are evaluated in the context of the scope and problems associated with disease entities in women. Nonhuman primate research with known information regarding women's disease is discussed, and the utility of the animal model for the study of human disease is highlighted, based on its significant relevance due to similarities of nonhuman primate and human subjects' physiology, metabolism, and responses to therapeutic interventions. Additional advantages of the animal model include the ability to control the experimental environment and the capacity to perform chronic study procedures. These findings allow us to utilize the nonhuman primate as the most relevant model in the animal world for the study of human disease processes.     

Progress and challenges in therapies for AIDS in nonhuman primate models

Efforts to develop animal models for human immunodeficiency virus type-1 (HIV-1) vaccine testing have focused on lentivirus infection of nonhuman primates. A long-term goal of this primate research is to utilize the models to understand the mechanisms of pathogenesis leading to AIDS. Because the time to disease is compressed relative to HIV infection in humans, therapeutic strategies and compounds can be tested in nonhuman primate models in a shorter time frame and under more controlled conditions than are possible in many clinical studies. Recent interventive studies in primates using antiviral drugs or passive immune globulin (IgG) have demonstrated that multiple log reductions in plasma virus can be achieved and sustained, with accompanying health benefits. Information gained about timing and dosage may be of utility in designing clinical studies. The development of reliable and predictable animal models for effective therapies and vaccines against AIDS remains a critical priority for primate research.     

Celebrating a life by recognizing realities

This special issue on nonhuman primate behavior and welfare, the proceedings of a special Animal Behavior Society session, celebrates the life of Dr. Sylvia Taylor (1963-2005). Sylvia's premature death reminded her friends to recognize the reality that life is short, but one can make the most of it. Many individuals and organizations have also recognized the reality that an educational venture such as this one requires adequate funding and support. Their generosity has made this undertaking a success. The idea behind the session was to recognize the reality that one cannot ensure nonhuman animal welfare without understanding animal behavior, and to explore the ways in which this principle applies to primates. One must also recognize the reality that nonhuman primate welfare depends on understanding the behavior of the human primate as well as the nonhuman primate. Ensuring the welfare of the nonhuman primate sometimes requires educating and motivating the human primate. This special issue will hopefully provide helpful information to increase the reader's knowledge of primate behavior and welfare and to help the reader educate others on these important topics.     

Generation of transgenic monkeys with human inherited genetic disease

Modeling human diseases using nonhuman primates including chimpanzee, rhesus, cynomolgus, marmoset and squirrel monkeys has been reported in the past decades. Due to the high similarity between nonhuman primates and humans, including genome constitution, cognitive behavioral functions, anatomical structure, metabolic, reproductive, and brain functions; nonhuman primates have played an important role in understanding physiological functions of the human body, clarifying the underlying mechanism of human diseases, and the development of novel treatments for human diseases. However, nonhuman primate research has been restricted to cognitive, behavioral, biochemical and pharmacological approaches of human diseases due to the limitation of gene transfer technology in nonhuman primates. The recent advancement in transgenic technology that has led to the generation of the first transgenic monkey in 2001 and a transgenic monkey model of Huntington’s disease (HD) in 2008 has changed that focus. The creation of transgenic HD monkeys that replicate key pathological features of human HD patients further suggests the crucial role of nonhuman primates in the future development of biomedicine. These successes have opened the door to genetic manipulation in nonhuman primates and a new era in modeling human inherited genetic disorders. We focused on the procedures in creating transgenic Huntington’s disease monkeys, but our work can be applied to transgenesis in other nonhuman primate species.     

Use of primates in research: a global overview

We assessed the use of nonhuman primates and nonhuman primate biological material in research by reviewing studies published in 2001 in peer-reviewed journals. The number and species of primates used, the origin of the animals, the type of study, the area of research of the investigation, and the location at which the research was performed were tabulated. Additionally, factors related to the animals that may have affected the outcome of the experiments were recorded. A total of 2,937 articles involving 4,411 studies that employed nonhuman primates or nonhuman primate biological material were identified and analyzed. More than 41,000 animals were represented in the studies published in 2001. In the 14% of studies for which re-use could be determined, 69% involved animals that had been used in previous experiments. Published studies most commonly used nonhuman primates or nonhuman primate biological material from the species Chlorocebus aethiops (19%), Macaca mulatta (18%), M. fascicularis (9%), and Papio spp. (6%). Of these studies, 54% were classified as in vitro studies, 14% as noninvasive, 30% as chronic, and 1% were considered acute. Nonhuman primates were primarily used in research areas in which they appear to be the most appropriate models for humans. The most common areas of research were microbiology (including HIV/AIDS (26%)), neuroscience (19%), and biochemistry/chemistry (12%). Most (84%) of the primate research published in 2001 was conducted in North America, Europe, and Japan. The animals and conditions under which they were housed and used were rarely described. Although it is estimated that nonhuman primates account for an extremely small fraction of all animals used in research, their special status makes it important to report the many husbandry and environmental factors that influence the research results generated. This analysis has identified that editors rarely require authors to provide comprehensive information concerning the subjects (e.g., their origin), treatment conditions, and experimental procedures utilized in the studies they publish. The present analysis addresses the use of primates for research, including the effects of a shortage of suitable nonhuman primate subjects in many research areas.     

Celebrating a Life by Recognizing Realities

This special issue on nonhuman primate behavior and welfare, the proceedings of a special Animal Behavior Society session, celebrates the life of Dr. Sylvia Taylor (1963-2005). Sylvia's premature death reminded her friends to recognize the reality that life is short, but one can make the most of it. Many individuals and organizations have also recognized the reality that an educational venture such as this one requires adequate funding and support. Their generosity has made this undertaking a success. The idea behind the session was to recognize the reality that one cannot ensure nonhuman animal welfare without understanding animal behavior, and to explore the ways in which this principle applies to primates. One must also recognize the reality that nonhuman primate welfare depends on understanding the behavior of the human primate as well as the nonhuman primate. Ensuring the welfare of the nonhuman primate sometimes requires educating and motivating the human primate. This special issue will hopefully provide helpful information to increase the reader's knowledge of primate behavior and welfare and to help the reader educate others on these important topics.     

中国非人灵长类物种的行为偏侧研究进展

行为偏侧是指动物进行某一行为时偏好使用某一侧肢体或感觉器官。行为偏侧作为脑偏侧所对应的可观测的行为指标,是动物行为适应性进化的代表性特征之一,它在个体水平上影响着个体适合度,在群体水平上是社会性物种的一种进化稳定策略,具有重要的生态和进化意义。中国非人灵长类资源丰富,而中国非人灵长类的行为偏侧研究起步较晚,始于二十世纪八十年代。本文系统归纳中国非人灵长类物种的行为偏侧研究进展,并基于当前研究现状,为今后发展提出积极建议。     

Primate Communication: By Nature Honest, or by Experience Wise?

We review evolutionary views on honesty and deception and their application to studies of nonhuman primate communication. There is evidence that some primate signals are likely to be accurate on the basis of costliness. They appear most often in contexts that include overtly competitive interactions in which unrelated individuals have limited access to information about one another. However, both game theoretic models and most empirical work suggest that costly signals are not often likely to be the basis for honest communication in nonhuman primates. Inexpensive signaling can exist in contexts wherein communication occurs among related animals, something common among many nonhuman primate societies. Another condition in which inexpensive signaling is possible and that is also typical of nonhuman primates, is when sender and receiver both benefit from coordinated interactions. Additionally, when individuals interact repeatedly and can use past interactions to assess the honesty of signals and to modify future response to signals, low-cost signals can evolve. Nonhuman primates appear to deal with the problem of deception via skeptical responding, which can be largely accounted for by learning rules and the fact that they live in stable social groups and can recognize one another and recall past interactions.