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2014年  第35卷  第3期

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Special Issue for Primates and Animal Models of Human Diseases
Foreword
2014, 35(3): 161-162.
Mycobacterium tuberculosis (M.tb) and human immunodeficiency virus (HIV) co-infection has become a public health issue worldwide. Up to now, there have been many unresolved issues either in the clinical diagnosis and treatment of M.tb/HIV co-infection or in the basic understanding of the mechanisms for the impairments to the immune system by interactions of these two pathogens. One important reason for these unsolved issues is the lack of appropriate animal models for the study of M.tb/HIV co-infection. This paper reviews the recent development of research on the animal models of M.tb/HIV co-infection, with a focus on the non-human primate models.
Postpartum depression (PPD) is a modified form of major depressive disorders (MDD) that can exert profound negative effects on both mothers and infants than MDD. Within the postpartum period, both mothers and infants are susceptible; but because PPD typically occurs for short durations and has moderate symptoms, there exists challenges in exploring and addressing the underlying cause of the depression. This fact highlights the need for relevant animal models. In the present study, postpartum adult female cynomolgus monkeys (Macaca fascicularis) living in breeding groups were observed for typical depressive behavior. The huddle posture behavior was utilized as an indicator of behavioral depression postpartum (BDP) as it has been established as the core depressive-like behavior in primates. Monkeys were divided into two groups: A BDP group (n=6), which were found to spend more time huddling over the first two weeks postpartum than other individuals that formed a non-depression control group (n=4). The two groups were then further analyzed for locomotive activity, stressful events, hair cortisol levels and for maternal interactive behaviors. No differences were found between the BDP and control groups in locomotive activity, in the frequencies of stressful events experienced and in hair cortisol levels. These findings suggested that the postpartum depression witnessed in the monkeys was not related to external factors other than puerperium period. Interestingly, the BDP monkeys displayed an abnormal maternal relationship consisting of increased infant grooming. Taken together, these findings suggest that the adult female cynomolgus monkeys provide a natural model of behavioral postpartum depression that holds a number of advantages over commonly used rodent systems in PPD modeling. The cynomolgus monkeys have a highly-organized social hierarchy and reproductive characteristics without seasonal restriction—similar to humans—as well as much greater homology to humans than rodents. As such, this model may provide a greater translational efficiency and research platform for systematically investigating the etiology, treatment, prevention of PPD.
In this study, we analyzed diffusion tensor imaging (DTI) results of brain white matter in rhesus macaques (Macaca mulatta) with four different parameter settings and found that the sequence A (b=1 000 s/mm2, spatial resolution=1.25 mm×1.25 mm× 1.25 mm, numbers of direction=33, NSA=3) and B (b=800 s/mm2, spatial resolution=1.25 mm×1.25 mm×1.25 mm, numbers of direction=33, NSA=3) could accurately track coarse fibers. The fractional anisotropy (FA) derived from sequence C (b=1 000s/mm2, spatial resolution=0.55 mm×0.55 mm×2.5 mm, direction number=33, NSA=3) was too fuzzy to be used in tracking white matter fibers. By comparison, the high resolution and the FA with high contrast of gray matter and white matter derived from sequence D (b=800 s/mm2, spatial resolution=1.0 mm×1.0 mm ×1.0 mm, numbers of direction=33, NSA=3) qualified in its application in tracking both thick and thin fibers, making it an optimal DTI setting for rhesus macaques.
The northern pig-tailed macaque (Macaca leonina) has been identified as an independent species of Old World monkey, and we previously found that PBMCs from M. leonina were susceptible to human immunodeficiency virus type 1 (HIV-1), which may be due to the absence of a TRIM5 protein restricting HIV-1 replication. Here we investigated the infection potentials of six laboratory adapted HIV-1 strains and three primary HIV-1 isolates in PBMCs from M. leonina. The results indicate that these strains are characterized by various but low replication levels, and among which, HIV-1NL4-3 shows the highest replication ability. Based on the abundant evidence of species-specific interactions between restriction factors APOBEC3 and HIV/SIV-derived Vif protein, we subsequently examined the replication potentials of vif-substituted HIV-1 (HSIV) in M. leonina PBMCs. Notably, HSIV-vifmac and stHIV-1SV chimeras, two HIV-1NL4-3-derived viruses encoding the viral infectivity factor (Vif) protein from SIVmac239, replicated robustly in cells from M. leonina, which suggests that HSIV could effectively antagonize the antiviral activity of APOBEC3 proteins expressed in cells of M. leonina. Therefore, our data demonstrate that M. leonina has the potential to be developed into a promising animal model for human AIDS.
The northern pig-tailed macaque (NPM,Macaca leonina) has become a widely used animal model in biomedical research. In this study, we measured serum immunoglobulin IgG, IgM, IgA, complement C3, C4 and CRP levels in 3-11 year old captive northern pig-tailed macaques using HITACHI 7600-20 automated chemistry analyzer in order to determine the influences of age and gender on these items. The results showed that serum IgA, IgM, C3 and C4 levels were not correlated with age (P>0.05), while serum IgG levels increased progressively with age (r=0.202;P=0.045). Serum IgG, IgA, IgM and C3 levels were higher in females than in males (P<0.05). Moreover, serum C3 concentration was both positively and strongly correlated with that of C4 (r=0.700; P<0.0001). This study provides basic serum immunoglobulin and complement data of captive northern pig-tailed macaques, which may prove useful for future breeding efforts and biomedical research.
Different types of dominance hierarchies reflect different social relationships in primates. In this study, we clarified the hierarchy and social relationships in a one-male unit of captive Rhinopithecus bieti observed between August 1998 and March 1999. Mean frequency of agonistic behaviour among adult females was 0.13 interactions per hour. Adult females exhibited a linear hierarchy with a reversal of 10.9%, indicating an unstable relationship; therefore, R. bieti appears to be a relaxed/tolerant species. The lack of a relationship between the agonistic ratio of the adult male towards adult females and their ranks indicated that males did not show increased aggression towards low-ranking females. Differentiated female affiliative relationships were loosely formed in terms of the male, and to some extent influenced by female estrus, implying that relationships between the male and females is influenced by estrus and not rank alone. A positive correlation between the agonistic ratio of adult females and their ranks showed that the degree to which one female negatively impacted others decreased with reduction in rank. Similarly, a positive correlation between the agonistic ratio of females and differences in rank suggests that a female had fewer negative effects on closely ranked individuals than distantly ranked ones. These data indicate that rank may influence relationships between females. A steeper slope of regression between the agonistic ratio and inter-female rank differences indicated that the extent of the power difference in high-ranking females exerting negative effects on low-ranking ones was larger during the mating season than the birth season, suggesting that rank may influence the mating success of females.
Self-directed behavior (SDB) is characterized as an indicator of anxiety, frustration and stress in nonhuman primates. In this study, we collected self-directed behavior data from one group of free-ranging Tibetan macaques (Macaca thibetana) at Mt. Huangshan, China (September 2012–May 2013) using a combination of behavioral sampling methods including focal animal sampling, behavioral sampling, continuous sampling and instantaneous sampling. Our results showed that females engaged in significantly higher rates of self-directed behavior when they were in proximity to dominant individuals compared to subordinate ones. Conflict losers significantly increased their SDB rates after agonistic episodes, indicating that SDB might also serve as an index of anxiety in M. thibetana. We further found that females significantly increased their SDB rates when focal individual was proximity to weakly affiliation relationship higher rank members than to strongly affiliation relationship higher rank members. If conflicts were not reconciled, the postconflict SDB rates of losers were higher when they stayed with strongly affiliation opponents; if conflicts were reconciled, victims of strongly affiliation relationships opponents engaged in more SDB rates before reconciliation than after reconciliation, while victims of moderately affiliation relationships opponents did not engaged in more SDB rates before reconciliation than after reconciliation. We conclude that both of dominance rank and affiliation relationships might both influence the SDB rates of female Tibetan macaques significantly, suggesting that SDB is not only an index of anxiety in Tibetan macaques, but also can provide a new insight into evaluation of social relationships between individuals.
Adult male Tibetan (Macaca thibetana), Barbary (M. sylvanus), and stump-tailed macaques (M. arctoides) engage in bridging, a ritualized infant-handling behavior. Previous researchers found a bias toward the use of male infants for this behavior, but its function is debated. Explanations include three hypotheses: paternal care, mating effort, and agonistic buffering. We studied a group of habituated, provisioned Tibetan macaques to test whether adult males' affiliative relationships with females predicted their use of an infant for bridging. We also examined biases for sex, age, and individual in males' choice of bridging infant. We collected data via all occurrences, focal animal, and scan methods, from August to September 2011 at the Valley of the Wild Monkeys, China. We found that male infants were significantly preferred over females for bridging, but of three male infants in the group, only one was used by all males, while one male infant was used less often than expected. Adult males had females they were significantly more likely to be proximate to and/or to groom, but these corresponded to the mother of the bridging infant for only one male. Our results are most consistent with the agonistic buffering hypothesis: lower-ranked males used the alpha male's preferred bridging infant in an attempt to regulate their interactions with the alpha.
In this study, the quadrat method was used to study the effects of tsaoko (Fructus tsaoko) plantation on tree diversity and canopy structure of two natural habitats of eastern hoolock gibbon (Hoolock leuconedys): Nankang (characterized by extensive tsaoko plantation) and Banchang (relatively well reserved and without tsaoko plantation). Totally, 102 tree species from 25 families and 16 woody liana species from 10 families were recorded in Nankang, whereas 108 tree species from 30 families and 17 woody liana species from 12 families were recorded in Banchang. Although the tree species between two habitats is different, both habitats are characterized by enriched food resources for eastern hoolock gibbons, sharing similar dominant plant families. Due to tsaoko plantation, tree density proportion and diversity of forest layerⅠ (>20 m) in Nankang were both significantly decreased, but the tree density of layerⅡ (10-20 m) increased. Likewise, in conjunction with these behavioral observations, we also address potential impacts of tsaoko plantation on the behavior of eastern hoolock gibbon.
While the recent release of the Chinese tree shrew (Tupaia belangeri chinensis) genome has made the tree shrew an increasingly viable experimental animal model for biomedical research, further study of the genome may facilitate new insights into the applicability of this model. For example, though the tree shrew has a rapid rate of speed and strong jumping ability, there are limited studies on its locomotion ability. In this study we used the available Chinese tree shrew genome information and compared the evolutionary pattern of 407 locomotion system related orthologs among five mammals (human, rhesus monkey, mouse, rat and dog) and the Chinese tree shrew. Our analyses identified 29 genes with significantly high ω (Ka/Ks ratio) values and 48 amino acid sites in 14 genes showed significant evidence of positive selection in the Chinese tree shrew. Some of these positively selected genes, e.g. HOXA6 (homeobox A6) and AVP (arginine vasopressin), play important roles in muscle contraction or skeletal morphogenesis. These results provide important clues in understanding the genetic bases of locomotor adaptation in the Chinese tree shrew.