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A natural model of behavioral depression in postpartum adult female cynomolgus monkeys (Macaca fascicularis)

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Zoological Research 2014年第3期35卷 174-181页

作者： Xun-Xun CHU joshua dominic rizak Shang-Chuan YANG Jian-Hong WANG Yuan-Ye MA Xin-Tian HU Laboratory of Primate Neuroscience Research and Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences& Yunnan Province Kunming Institute of Zoology University of the Chinese Academy of Sciences Kunming Primate Research Center Kunming Institute of Zoology Chinese Academy of Sciences

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 t3DP 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

关键词： Postpartum depression Cynomolgus monkeys Huddle behavior Locomotion activity Stressful events Hair cortisol Maternal relationship

Social rank and cortisol among female rhesus macaques(Macaca mulatta)

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Zoological Research 2013年第2期34卷 42-49页

作者： Dong-Dong QIN joshua dominic rizak Xiao-Li FENG Xun-Xun CHU Shang-Chuan YANG Chun-Lu LI Long-Bao LV Yuan-Ye MA Xin-Tian HU Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences&Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China University of Chinese Academy of Sciences Beijing 100049China Institute of Psychology Chinese Academy of SciencesBeijing 100101China Kunming Primate Research Center Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China State Key Laboratory of Brain and Cognitive Sciences Institute of BiophysicsChinese Academy of SciencesBeijing 100101China

In animal societies,some stressful events can lead to higher levels of physiological *** stressors,like social rank,also predict an increased vulnerability to an array of ***,the physiological relationship between social rank and stress varies between different species,as well as within groups of a single *** example,dominant individuals are more socially stressed at times,while at other times it is the subordinate ones who experience this ***,these variations make it difficult to assess disease vulnerability as connected to social *** order to learn more about how physiological rank relationships vary between groups of a single species,cortisol measurements from hair samples were used to evaluate the effects of dominance rank on long-term stress levels in despotic and less stringent female rhesus macaque hierarchal *** despotic groups,cortisol levels were found not to be correlated with social rank,but a negative correlation was found between social rank and cortisol levels in less stringent *** ranking monkeys in less stringent groups secreted elevated levels of cortisol compared to higher ranking *** data suggest that variations in the strictness of the dominance hierarchy are determining factors in rank related stress *** further consideration of nonhuman primate social system diversity and the linear degree of their hierarchies may allow for the development of valid rank-related stress models that will help increase our understanding and guide the development of new therapeutics for diseases related to human socioeconomic status.

关键词： Social rank Hypothalamus-pituitary-adrenal axis Cortisol Female Rhesus macaques

Feature-reduction and semi-simulated data in functional connectivity-based cortical parcellation

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Neuroscience Bulletin 2013年第3期29卷 333-347页

作者： Xiaoguang Tian Cirong Liu Tianzi Jiang joshua rizak Yuanye Ma Xintian Hu Kunming Institute of Zoology Chinese Academy of Sciences The University of Queensland Queensland Brain Institute LIAMA Center for Computational Medicine National Laboratory of Pattern Recognition Institute of Automation Chinese Academy of Sciences Yunnan Key Lab of Primate Biomedical Research State Key Laboratory of Brain and Cognitive Science Institute of Biophysics Chinese Academy of Sciences Kunming Bio-International

Recently, restingstate functional magnetic resonance imaging has been used to parcellate the brain into functionally distinct regions based on the information available in functional connectivity maps. However, brain voxels are not independent units and adjacent voxels are always highly correlated, so functional connectivity maps contain redundant information, which not only impairs the computational efficiency during clustering, but also reduces the accuracy of clustering results. The aim of this study was to propose featurereduction approaches to reduce the redundancy and to develop semisimulated data with defined ground truth to evaluate these approaches. We proposed a featurereduction approach based on the Affinity Propagation Algorithm （APA） and compared it with the classic feature reduction approach based on Principal Component Analysis （PCA）. We tested the two approaches to the parcellation of both semisimulated and real seed regions using the Kmeans algorithm and designed two experiments to evaluate their noise resistance. We found that all functional connectivitymaps （with/without feature reduction） provided correct information for the parcellation of the semi simulated seed region and the computational efficiency was greatly improved by both feature reduction approaches. Meanwhile, the APAbased featurereduction approach outperformed the PCA based approach in noiseresistance. The results suggested that functional connectivity maps can provide correct information for cortical parcellation, and featurereduction does not significantly change the information. Considering the improvement in computational efficiency and the noiseresistance, featurereduction of functional connectivity maps before cortical parcellation is both feasible and necessary.

关键词： cortical parcellation resting-state fMRI functional connectivity feature reduction stimulateddata AP algorithm

Interactive effects of morphine and dopaminergic compounds on spatial working memory in rhesus monkeys

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Neuroscience Bulletin 2013年第1期29卷 37-46页

作者： Jian-Hong Wang joshua Dominie rizak Yan-Mei Chen Liang Li Xin-Tian Hu Yuan-Ye Ma State Key Laboratory of Brain and Cognitive Sciences Kunming Institute of Zoology Chinese Academy of Sciences Graduate University of Chinese Academy of Sciences Department of Psychology Speech and Hearing Research Center Key Laboratory on Machine Perception (Ministry of Education) Peking University

Opiates and dopamine （DA） play key roles in learning and memory in humans and animals. Although interactions between these neurotransmitters have been found, their functional roles remain to be fully elucidated, and their dysfunction may contribute to human diseases and addiction. Here we investigated the interactions of morphine and dopaminergic neurotransmitter systems with respect to learning and memory in rhesus monkeys by using the Wisconsin General Test Apparatus （WGTA） delayed-response task. Morphine and DA agonists （SKF-38393, apomorphine and bromocriptine） or DA antagonists （SKF-83566, haloperidol and sulpiride） were co-administered to the monkeys 30 min prior to the task. We found that dose-patterned co-administration of morphine with D1 or D2 antagonists or agonists reversed the impaired spatial working memory induced by morphine or the compounds alone. For example, morphine at 0.01 mg/kg impaired spatial working memory, while morphine （0.01 mg/kg） and apomorphine （0.01 or 0.06 mg/kg） co-treatment ameliorated this effect. Our findings suggest that the interactions between morphine and dopaminergic compounds influence spatial working memory in rhesus monkeys. A better understanding of these interactive relationships may provide insights into human addiction.

关键词： working memory morphine dopamine rhesus monkey

Combined action of MK-801 and ceftriaxone impairs the acquisition and reinstatement of morphine-induced conditioned place preference,and delays morphine extinction in rats

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Neuroscience Bulletin 2012年第5期28卷 567-576页

作者： Yaodong Fan Haichen Niu joshua D. rizak Ling Li Guimei Wang Liqi Xu He Ren Hao Lei Hualin Yu Department of Neurosurgery the Third Affiliated Hospital of Kunming Medical University Kunming 650118 China State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics Wuhan Institute of Physics and Math-ematics Chinese Academy of Sciences Wuhan 430071 China State Key Laboratory of Brain and Cognitive Sciences Kunming Institute of Zoology Chinese Academy of Sciences Kunming 650223 China Department of Medical Imaging Kunming General Hospital of Chengdu Military Region People's Liberation Army Kunming 650032 China Minimally Invasive Neurosurgery Department the First Affiliated Hospital of Kunming Medical University Kunming 650032 China

Objective It is well established that glutamate and its receptors, particularly the N-methyl-D-aspartate receptor （NMDAR）, play a significant role in addiction and that the inhibition of glutamatergic hyperfunction reduces addictive behaviors in experimental animals. Specifically, NMDAR antagonists such as MK-801, and an inducer of the expression of glutamate transporter subtype-1 （GLT-1）（ceftriaxone） are known to inhibit addictive behavior. The purpose of this study was to determine whether the combined action of a low dose of MK-801 and a low dose of ceftriaxone provides better inhibition of the acquisition, extinction, and reinstatement of morphine-induced conditioned place preference （CPP） than either compound alone. Methods A morphine-paired CPP experiment was used to study the effects of low doses of MK-801, ceftriaxone and a combination of both on reward-related memory （acquisition, extinction, and reinstatement of morphine preference） in rats. Results A low dose of neither MK-801 （0.05 mg/kg, i.p.） nor ceftriaxone （25 mg/kg, i.p.） alone effectively impaired CPP behaviors. However, when applied in combination, they reduced the acquisition of morphine-induced CPP and completely prevented morphine reinstatement. Their combination also notably impaired the extinction of morphine-induced CPP. Conclusion The combined action of a low dose of an NMDAR antagonist （MK-801） and GLT-1 activation by ceftriaxone effectively changed different phases of CPP behavior.

关键词： ceftriaxone conditioned place preference morphine MK-801 glutamate transporter subtype-1

A cynomolgus monkey with naturally occurring Parkinson's disease

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National Science Review 2021年第3期8卷 17-20页

作者： Hao Li Ling-Yan Su Lixin Yang Min Li Qianjin Liu Zhenhui Li Yan Hu Hongwei Li Shihao Wu Wenchao Wang Yingzhou Hu Zhengbo Wang joshua D.rizak Baihui Huang Min Xu Jing Wu Long-Bao Lv Christoph W.Turck Yong Yin Yong-Gang Yao Bing Su Xintian Hu Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province Kunming Institute of Zoology Chinese Academy of Sciences State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Shenzhen Key Laboratory for Molecular Biology of Neural Development Guangdong Provincial Key Laboratory of Brain Connectome and Behavior CAS Key Laboratory of Brain Connectome and Manipulation The Brain Cognition and Brain Disease Institute Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences China Kunming College of Life Science University of Chinese Academy of Sciences Institute of Neuroscience CAS Key Laboratory of Primate Neurobiology State Key Laboratory of NeuroscienceChinese Academy of Sciences National Resource Center for Non-Human Primates Kunming Primate Research Center and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) Kunming Institute of Zoology Chinese Academy of Sciences Max Planck Institute of Psychiatry Department of Translational Research in Psychiatry Department of Rehabilitation Medicine the Second People’s Hospital of Yunnan Province Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences KIZ–CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases Kunming Institute of Zoology Chinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences

Evidence for the existence of monkeys with spontaneous Parkinson’s disease (PD) has been lacking. Here,we screened macaque colonies at the Kunming Primate Research Center(Association for Assessment and Accreditation of Laboratory Animal Care(AAALAC) accredited), Kunming Institute of Zoology, Chinese Academy of Sciences, which has a large population of monkeys (>2400), to identify naturally occurring PD monkeys.

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Comparative study of the transfection efficiency of commonly used viral vectors in rhesus monkey (Macaca mulatta) brains

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Zoological Research 2017年第2期38卷 88-95页

作者： Shi-Hao Wu Zhi-Xing Liao joshua D. rizak Na Zheng Lin-Heng Zhang Hen Tang Xiao-Bin He Yang Wu Xia-Ping He Mei-Feng Yang Zheng-Hui Li Dong-Dong Qin Xin-Tian Hu Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan 650223 China Nerve System Coding Discipline Group Kunming College of Life Science University of the Chinese Academy of Sciences Kunming Yunnan 650000 China Kunming Primate Research Center Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan 650223 China Department of Anatomy and Histology & Embryology Faculty of Basic Medical Science Kunming Medical University Kunming Yunnan 650500 China CAS Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences Shanghai 200031 China Center for Excellence in Brain Science Wuhan Institute of Physics and Mathematics Chinese Academy of Sciences Wuhan Hubei 430071 China

Viral vector transfection systems are among the simplest of biological agents with the ability to transfer genes into the central nervous system. In brain research, a series of powerful and novel gene editing technologies are based on these systems. Although many viral vectors are used in rodents, their full application has been limited in non-human primates. To identify viral vectors that can stably and effectively express exogenous genes within non- human primates, eleven commonly used recombinant adeno-associated viral and lentiviral vectors, each carrying a gene to express green or red fluorescence, were injected into the parietal cortex of four rhesus monkeys. The expression of fluorescent cells was used to quantify transfection efficiency. Histological results revealed that recombinant adeno-associated viral vectors, especially the serotype 2/9 coupled with the cytomegalovirus, human synapsin I, or Ca2~/calmodulin-dependent protein kinase II promoters, and lentiviral vector coupled with the human ubiquitin C promoter, induced higher expression of fluorescent cells, representing high transfection efficiency. This is the first comparison of transfection efficiencies of different viral vectors carrying different promoters and serotypes in non-human primates （NHPs）. These results can be used as an aid to select optimal vectors to transfer exogenous genes into the central nervous system of non-human primates.

关键词： Recombinant adeno-associated virus Lentivirus Rhesus monkey Central nervous system

What interests them in the pictures? — Differences in eyetracking between rhesus monkeys and humans

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Neuroscience Bulletin 2013年第5期29卷 553-564页

作者： Ying-Zhou Hu Hui-Hui Jiang Ci-Rong Liu Jian-Hong Wang Cheng-Yang Yu Synnve Carlson Shang-Chuan Yang Veli-Matti Saarinen joshua D rizak Xiao-Guang Tian Hen Tan Zhu-Yue Chen Yuan-Ye Ma Xin-Tian Hu State Key Laboratory of Brain and Cognitive Sciences and Key Laboratory of Animal Models and Human Disease Mechanisms Kunming Institute of Zoology Chinese Academy of Sciences University of Chinese Academy of Sciences Institute of Biomedicine/Physiology University of Helsinki Brain Research Unit Aalto University School of Science Kunming Primate Center Chinese Academy of Sciences

Studies estimating eye movements have demonstrated that non-human primates have fixation patterns similar to humans at the first sight of a *** the current study,three sets of pictures containing monkeys,humans or both were presented to rhesus monkeys and *** eye movements on these pictures by the two species were recorded using a Tobii eye-tracking *** found that monkeys paid more attention to the head and body in pictures containing monkeys,whereas both monkeys and humans paid more attention to the head in pictures containing *** humans always concentrated on the eyes and head in all the pictures,indicating the social role of facial cues in *** humans paid more attention to the hands than monkeys,both monkeys and humans were interested in the hands and what was being done with them in the *** may suggest the importance and necessity of hands for ***,monkeys scored lower in eye-tracking when fixating on the pictures,as if they were less interested in looking at the screen than *** locations of fixation in monkeys may provide insight into the role of eye movements in an evolutionary context.

关键词： eye-tracking rhesus monkey fixation gaze

MPP+恒河猴脑内立体定向注射完整和特异地损毁黑质纹状体多巴胺通路

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MPP+恒河猴脑内立体定向注射完整和特异地损毁黑质纹状体多巴胺通...