Voice processing in human and non-human primates

Humans share with non-human primates a number of voice perception abilities of crucial importance in social interactions, such as the ability to identify a conspecific individual from its vocalizations. Speech perception is likely to have evolved in our ancestors on the basis of pre-existing neural mechanisms involved in extracting behaviourally relevant information from conspecific vocalizations (CVs). Studying the neural bases of voice perception in primates thus not only has the potential to shed light on cerebral mechanisms that may be--unlike those involved in speech perception--directly homologous between species, but also has direct implications for our understanding of how speech appeared in humans. In this comparative review, we focus on behavioural and neurobiological evidence relative to two issues central to voice perception in human and non-human primates: (i) are CVs 'special', i.e. are they analysed using dedicated cerebral mechanisms not used for other sound categories, and (ii) to what extent and using what neural mechanisms do primates identify conspecific individuals from their vocalizations?     

Serological response of non-human primates to human melanoma disialoganglioside GD3

Summary The immunogenicity of the disialoganglioside, GD3, a melanoma-tumor-associated antigen, has been evaluated in non-human primates. Sera from four chimpanzees and two monkeys were evaluated for anti-GD3 antibody activity by solid-phase radioimmunoassay using GD3 and control gangliosides as targets. Serum from one monkey, immunized with cells from a melanoma cell line, was strongly reactive with GD3, having a titer of >2500. In contrast, serum from this animal was non-reactive with several other gangliosides including the structurally similar GM3. Anti-GD3 reactivity was also demonstrable, albeit in low titer, in the sera of an additional monkey and a chimpanzee. Each of these animals had likewise been immunized using cells from melanoma cell lines. On the basis of these observations, suggestive of a primate anti-GD3 antibody response, we initiated a series of immunizations of chimpanzee using purified GD3 bound to Salmonella minnesota, R595. IgG reactive with melanoma cells in the cell-binding assay was first detected in sera collected after 4 immunizations and increased in titer against each reactive melanoma cell line during the immunizations. Reactivity of this serum with melanoma cell lines demonstrated a direct correlation with the expression of GD3 by the respective cell line. Anti-GD3 reactivity was evident in solid-phase radioimmunoassay against purified GD3 beginning with serum collected after 11 immunizations. By comparison with its binding to the control ganglioside panel, this serum demonstrated strong specificity for GD3 (titer=640) while having only marginal reactivity with GM3 (titer=40). Immune serum from this animal was also able specifically to block subsequent binding of a murine IgM anti-GD3 antibody (DMab7) to target GD3 in solid-phase radioimmunoassay. Together, these observations suggest that GD3, in the form of a purified molecule bound to a bacterial matrix or as part of the intact melanoma cell membrane, can be immunogenic in non-human primates, and is able to elicit an antibody response of appropriate specificity.Supported in part by grant CA32672 from the National Cancer Institute, Veterans Administration Program 821 and by the Yerkes Regional Primate Center, Atlanta, Georgia. The Yerkes Center is fully accredited by the American Association for Accreditation of Laboratory Animal Care     

Eye contact by non-human primates toward a human observer

Eye contact by monkeys toward a staring observer is a quantifiable reliable and sensitive behavioural measure. Early social deprivation, an increase in age, a new cage, and an increase in distance all decreased the frequency of eye contact. Young female rhesus monkeys made more contact than young males. Large differences in eye contact occurred between species of non-human primates. The results are considered in relation to both an arousal theory and an attention theory.     

Evidence of adult neurogenesis in non-human primates and human

Adult neurogenesis in rodents has been extensively studied. Here, we briefly summarize the studies of adult neurogenesis based on non-human primate brains and human postmortem brain samples in recent decades. The differences between rodent, primate and human neurogenesis are discussed. We conclude that these differences may contribute to distinct physiological roles and the self-repair mechanisms in the brain across species.     

Immunopharmacology of recombinant human interleukin-18 in non-human primates

Recombinant human interleukin (IL)-18 (rHuIL-18) has a potential as a therapeutic agent in cancer and is currently in drug development. Since human IL-18 displays 96% and 100% amino acid sequence homology with cynomolgus monkey and chimpanzee IL-18, respectively, the biological responses to rHuIL-18 were evaluated in these species. A single intravenous dose of rHuIL-18 at 1 or 10mg/kg in cymonolgus monkeys caused a transient reduction in lymphocyte counts, induction of IL-1alpha and tumour necrosis factor alpha (TNF-alpha) mRNA in whole blood cells and a marked increase in plasma neopterin. rHuIL-18 administered to cynomolgus monkeys at doses of 0.3 or 3mg/kg for two 5-day cycles (Days 1-5 and 15-19) resulted in increased monocyte counts, induction of NK cells and concomitant increases in plasma IL-12 and neopterin. Administration of repeat doses of rHuIL-18 at 10mg/kg to chimpanzees was associated with increased monocyte counts, upregulation of FcgammaRI surface expression on monocytes, and increased IL-8, IL-12 and neopterin in plasma. These studies demonstrate, for the first time, the immunostimulatory activity of rHuIL-18 in vivo. The described pharmacological profile of rHuIL-18 in both cynomolgus monkeys and chimpanzees is indicative of the immunotherapeutic potential of rHuIL-18 in the treatment of cancer.     

In vivo protective anti-HIV immune responses in non-human primates through DNA immunization

Abstract: An effective immune response involves the specific recognition of and elimination of an infectious organism at multiple levels. In this context DNA immunization can present functional antigenic proteins to the host for recognition by all arms of the immune system, yet provides the opportunity to delete any genes of the infectious organism which code for antigens or pieces of antigens that may have deleterious effects. Our group has developed the use of nucleic acid immunization as a possible method of vaccination against Human immunodeficiency virus type 1 (HIV-1) [1,2,3,10,11,12]. Sera from non-human primates immunized with DNA vectors that express the envelope proteins from HIV-1 contain antibodies specific to the HIV-1 envelope. These sera also neutralize HIV-1 infection in vitro and inhibit cell to cell infection in tissue culture. Analysis of cellular responses is equally encouraging. T cell proliferation as well as cytotoxic T cell lysis of relevant env expressing target cells were observed. In addition, evidence that DNA vaccines are capable of inducing a protective response against live virus was demonstrated using a chimeric SIV/HIV (SHIV) challenge in vaccinated cynomologous macaques. We found that nucleic acid vaccination induced protection from challenge in one out of four immunized cynomolgus macaques and viral load was lower in the vaccinated group of animals versus the control group of animals. These data encouraged us to analyze this vaccination technique in chimpanzees, the most closely related animal species to man. We observed the induction of both cellular and humoral immune responses with a DNA vaccine in chimpanzees. These studies demonstrate the utility of this technology to induce relevant immune responses in primates which may ultimately lead to effective vaccines.     

Use of florfenicol in non-human primates

Studies were undertaken to determine if florfenicol, an antimicrobial agent structurally similar to chloramphenicol, could be used as an effective broad spectrum antibiotic for the treatment of bacterial infections in primates. Florfenicol was developed as an injectable antibiotic for use in cattle on an every other day dosing schedule. Its broad spectrum activity, long duration of action following i.m. administration, and its safety as compared with chloramphenicol made it an attractive antibiotic for use in non-human primates. Previous studies had shown that florfenicol is effective against common primate pathogens such as Salmonella, Klebsiella, Escherichia coli, Bordetella bronchiseptica, Streptococcus pneumoniae, Staphylococcus spp., and Yersinia pseudotuberculosis. We performed experiments on a total of 15 macaques. The animals were given florfenicol at 50 mg/kg i.m. and blood samples taken at various time points. Serum was evaluated for florfenicol absorption. Necropsies were also performed to determine if major organs were affected and to determine the effects of i.m. injection of florfenicol. We determined that florfenicol given every 48 hours in rhesus macaques results in blood levels that were acceptable for therapeutic use. The effect on muscle tissue of i.m. injection was similar to ketamine and normal saline. There were no gross lesions observed and no changes with tissues submitted for histology. Our work shows that with further studies, florfenicol may be useful when injectable antibiotic therapy is required in non-human primates.     

Noninvasive, transient and selective blood-brain barrier opening in non-human primates in vivo

The blood-brain barrier (BBB) is a specialized vascular system that impedes entry of all large and the vast majority of small molecules including the most potent central nervous system (CNS) disease therapeutic agents from entering from the lumen into the brain parenchyma. Microbubble-enhanced, focused ultrasound (ME-FUS) has been previously shown to disrupt noninvasively, selectively, and transiently the BBB in small animals in vivo. For the first time, the feasibility of transcranial ME-FUS BBB opening in non-human primates is demonstrated with subsequent BBB recovery. Sonications were combined with two different types of microbubbles (customized 4–5 µm and Definity®). 3T MRI was used to confirm the BBB disruption and to assess brain damage.     

Cortical control of grasp in non-human primates

The skilled use of the hand for grasping and manipulation of objects is a fundamental feature of the primate motor system. Grasping movements involve transforming the visual information about an object into a motor command appropriate for the coordinated activation of hand and finger muscles. The cerebral cortex and its descending projections to the spinal cord are known to play a crucial role for the control of grasp. Recent studies in non-human primates have provided some striking new insights into the respective contribution of the parietal and frontal motor cortical areas to the control of grasp. Also, new approaches allowed investigating the coupling of grasp-related activity in different cortical areas for the control of the descending motor command.     

Frequencies of oral pathologies in a sample of 767 non-human primates

In this work 767 skulls of both wild caught and captive non-human primates were studied and the following characteristics were analyzed: frequency of caries and osteolytic phenomena, presence of apical or radicular cysts, degree of bone atrophy and parodontal tissue alterations, neoplasies, supernumerary teeth, and cusps. Caries and osteolytic phenomena were more frequent in captive animals because of their “anthropic” diet, while frequency of dental fractures was higher in wild primates because of their higher environmental stress. The most frequent pathologies observed in non-human primates were tartar, parodontopathies, and condylar wear, while caries and osteolytic phenomena were minimal. Condylar wear was very frequent but not very marked and possibly due to “physiological” responses and not, as in humans, to a force unbalance which occurs in masticatory dynamics of the temporomandibular joint.