Effects of social subordination and oestradiol on resting‐state amygdala functional connectivity in adult female rhesus monkeys

Preclinical studies demonstrate that chronic stress modulates the effects of oestradiol (E2) on behaviour through the modification of the amygdala and the medial prefrontal cortex (mPFC) neuronal structure. Clinical studies suggest that alterations in amygdala functional connectivity (FC) with the mPFC may be associated with stress‐related phenotypes, including mood and anxiety disorders. Thus, identifying the effects of stress and E2 on amygdala‐mPFC circuits is critical for understanding the neurobiology underpinning the vulnerability to stress‐related disorders in women. In the present study, we used a well‐validated rhesus monkey model of chronic psychosocial stress (subordinate social rank) to examine effects of E2 on subordinate (SUB) (i.e. high stress) and dominant (DOM) (i.e. low stress) female resting‐state amygdala FC with the mPFC and with the whole‐brain. In the non‐E2 treatment control condition, SUB was associated with stronger left amygdala FC to subgenual cingulate (Brodmann area [BA] 25: BA25), a region implicated in several psychopathologies in people. In SUB females, E2 treatment strengthened right amygdala‐BA25 FC, induced a net positive amygdala‐visual cortex FC that was positively associated with frequency of submissive behaviours, and weakened positive amygdala‐para/hippocampus FC. Our findings show that subordinate social rank alters amygdala FC and the impact of E2 on amygdala FC with BA25 and with regions involved in visual processing and memory encoding.     

Evidence in primates supporting the use of chemogenetics for the treatment of human refractory neuropsychiatric disorders

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Sub-gingival microflora in Macaca mulatta species of rhesus monkey

The Macaca mulatta species of rhesus monkey is one of several non-human primate (nhp) models for periodontal disease. This report presents the bacteriology of the gingival sulci in M. mulatta monkeys. Three sub-gingival sites (maxillary right central incisor, the disto-buccal of the mandibular left second molar and mesio-buccal of the mandibular right second molar) of 9 monkeys were evaluated clinically before scaling and 7 days after scaling. Plaque samples were obtained from sub-gingival sites before clinical examination and studied bacteriologically by dark field microscopy, selective and non-selective culture, and by primary phenotypic characterizations of culture isolates. Several gingival sites presented with mild gingival inflammation. Anaerobic and facultatively anaerobic bacteria were the predominant flora colonizing the gingival sulci. The major microbial groups were Haemophilus species (100% of sites; percentage of total anaerobic count (TAC); 21-51), Peptostreptococcus micros (89%, 7.5–29.5), Actinomyces sp. (85%, 7–27), Fusobacterium nucleatum (90%, 5–8), Actinobacillus actinomycetemcomitans (73%, 1.3–12), black-pigmented anaerobic rods ( BPAR ) (80%, 0.6–6.5) and oral streptococci (80%, 0.2–1.0). Microbial groups detected less often were Wolinella sp. (66%, 0–2.6), Capnocytophaga sp. (30%), Eikenella corrodens (4.7%, 0), Campylobacter sp. (28%, 0–0.1) and spirochetes (4.7%, 0–0.07). Seven days after gingival sites were scaled, the plaque score and indices for gingival inflammation declined significantly. The gingival flora after scaling were characterized by lower proportions of the Actinomyees sp., P. micros and BPAR; and increased proportions of the oral streptococci, relative to pre-scaling levels. The major microbial groups at scaled gingival sites were the Haemophilus sp., oral streptococci, F. nucleatum and A. actinomycetemcomitans. The mutual proportions of microbial groups varied non-significantly within gingival sites and between monkeys. In conclusion, the M. mulatta gingival sulci are colonized by microbial species that resemble putative pathogens of periodontal disease, and the composition and character of the gingival flora are similar to the gingival flora of other Old World monkey models.     

超声引导股动脉穿刺置管在血管内介入方法制备恒河猴急性脑梗死模型中的应用

目的 探讨超声引导股动脉穿刺置管在血管内介入方法制备恒河猴急性脑梗死模型中的应用效果。 方法 选择拟行大脑中动脉M2段栓塞建模的健康成年恒河猴16只,雄性,采用数字表法随机分为2组(n=8):对照组(C组)、超声引导组(U组)。所有恒河猴采用0.1 mL/kg氯胺酮及速眠新的混合液肌内注射进行基础麻醉,待动物入睡后行气管内插管,接呼吸机行机械通气,麻醉维持采用持续输注丙泊酚(5~8 mg·kg^-1·h^-1)。C组采用传统指尖触摸法进行股动脉穿刺置管,U组采用超声引导平面内-平面外联合法进行股动脉穿刺置管。比较两组1次、2次穿刺置管成功率、总成功率、穿刺置管次数、穿刺置管花费时间及并发症发生率。结果 C组与U组1次穿刺置管成功率分别为25.0%和62.5%,2次穿刺置管成功率分别为50.0%和87.5%、总成功率分别为75.0%和100%。C组与U组穿刺置管次数分别为(3.0±1.6)次和(1.5±0.8)次,穿刺置管花费时间分别为(15.8±6.1) min和(5.4±2.9)min。与C组比较,U组穿刺置管次数少,穿刺置管花费时间较短,两组差异有统计学意义(P<0.05);与C组比较,U组1次、2次穿刺置管成功率及总成功率均较高,但差异无统计学意义(P>0.05)。两组股动脉穿刺置管并发症发生率比较差异无统计学意义(P>0.05)。结论 在血管内介入方法制备恒河猴急性脑梗死模型中,采用平面内-平面外联合技术进行超声引导股动脉穿刺,可提高首次穿刺置管成功率及总成功率,减少穿刺置管次数,缩短穿刺置管花费时间。     

衰老动物模型的研究及其在抗衰老药物活性筛选中的应用

衰老以及衰老相关疾病使得人类生活的负担逐年加重。延缓衰老、减少衰老相关疾病的发生是解决问题的根源。动物模型是衰老研究的重要工具,就酵母、线虫、果蝇、斑马鱼、快速老化小鼠、D-半乳糖衰老模型、恒河猴等多种衰老研究中常用动物模型的特点及其在抗衰老药物筛选中的应用进展进行归纳总结,为衰老研究中相关动物模型的选择提供依据。     

Variation at the mu-opioid receptor gene (OPRM1) influences attachment behavior in infant primates

In a variety of species, development of attachment to a caregiver is crucial for infant survival and partly mediated by the endogenous opioids. Functional mu-opioid receptor gene polymorphisms are present in humans (OPRM1 A118G) and rhesus macaques (OPRM1 C77G). We hypothesized that rhesus infants carrying a gain-of-function OPRM1 77G allele would experience increased reward during maternal contact and would, therefore, display increased measures of attachment. We collected behavioral data from rhesus macaques (n = 97) during early infancy and at 6 months of age, across four cycles of maternal separation (4 days) and reunion (3 days). Animals were genotyped for the OPRM1 C77G polymorphism, and the effects of this allele on attachment-related behaviors were analyzed. Infants carrying the G allele exhibited higher levels of attachment behavior during early infancy. During prolonged periods of maternal separation, although infant macaques homozygous for the C allele exhibited decreases in their levels of distress vocalization with repeated separation, this response persisted in G allele carriers. The OPRM1 77G allele also affected social preference during reunion. C/G infants spent increasing amounts of time in social contact with their mothers as a function of repeated separation and were less likely to interact with other individuals in the social group, a pattern not observed among infants with the C/C genotype. These findings suggest a role for OPRM1 variation in the expression of attachment behavior in human subjects, especially as a function of separation from the caregiver.     

阿达木单抗类似药SMMU-16皮下注射对食蟹猴的重复给药毒性研究

目的：探讨阿达木单抗类似药SMMU-16重复皮下注射对食蟹猴的安全性。方法30只健康食蟹猴按体重随机分为溶媒对照组,阳性对照组,SMMU-16低、中、高剂量组,其中SMMU-16低、中、高剂量组分别给予SMMU-1610、33、200 mg/kg,每组6只,雌雄各半。阳性对照组给予33.0 mg/kg 阿达木单抗,溶媒对照组给予SM-MU-16空白溶液。给药体积均为4.0 ml/kg（分4个点注射）。每周1次皮下注射给药,共给药4周,恢复期4周,期间进行各项毒理学指标检测。结果与自身给药前（d0）相比,给药期间中剂量组、高剂量组及阳性对照组的红细胞计数、Hb定量、红细胞压积（HCT）降低（P均＜0.05）,中、高剂量组网织红细胞比例升高（P＜0.05）。骨髓检查发现SM-MU-16中、高剂量组及阳性对照组食蟹猴骨髓红细胞系轻度增生。组织病理学检查发现d28时阳性对照组和高剂量组各3只、中剂量组2只动物出现胸腺萎缩和脾脏萎缩。上述变化在恢复期结束时可逐渐恢复。各组动物肝脏和肾脏未见明显病理改变。其余指标包括一般症状、呼吸、体温、瞳孔、尿液、心电图、免疫和生化指标等未见明显与供试品相关的异常变化和量效、时效关系。结论 SMMU-16主要毒性靶器官为免疫系统（胸腺和脾脏）和血液系统,毒性作用具有一定的可逆性。此毒性作用考虑与SMMU-16免疫抑制药理作用的延伸和放大有关。SMMU-16皮下注射对食蟹猴的无毒性剂量为10 mg/kg。 SMMU-16与等剂量阳性对照药在本实验条件下出现的毒性反应基本类似。