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BMAL1 knockout macaque monkeys display reduced sleep and psychiatric disorders

National Science Review 2019年第1期6卷 87-100页

作者： Peiyuan Qiu Jian Jiang Zhen Liu Yijun Cai Tao Huang Yan Wang Qiming Liu Yanhong Nie Fang Liu Jiumu Cheng Qing Li Yun-Chi Tang Mu-ming Poo Qiang Sun Hung-Chun Chang Institute of Neuroscience State Key Laboratory of Neuroscience CAS Key Laboratory of Primate NeurobiologyCAS Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences Shanghai Research Center for Brain Science and Brain-inspired Technology Dynamic Brain Signal Analysis Facility Institute of NeuroscienceChinese Academy of Sciences CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health Shanghai Institutes for Biological SciencesUniversity of Chinese Academy of Sciences College of Life Sciences University of Chinese Academy of Sciences

Circadian disruption is a risk factor for metabolic, psychiatric and age-related disorders, and non-human primate models could help to develop therapeutic treatments. Here, we report the generation of BMAL1 knockout cynomolgus monkeys for circadian-related disorders by CRISPR/Cas9 editing of monkey embryos. These monkeys showed higher nocturnal locomotion and reduced sleep, which was further exacerbated by a constant light regimen. Physiological circadian disruption was reflected by the markedly dampened and arrhythmic blood hormonal levels. Furthermore, BMAL1-deficient monkeys exhibited anxiety and depression, consistent with their stably elevated blood cortisol, and defective sensory processing in auditory oddball tests found in schizophrenia patients. Ablation of BMAL1 up-regulated transcriptional programs toward inflammatory and stress responses, with transcription networks associated with human sleep deprivation, major depressive disorders, and aging. Thus, BMAL1 knockout monkeys are potentially useful for studying the physiological consequences of circadian disturbance, and for developing therapies for circadian and psychiatric disorders.

关键词： circadian rhythms BMAL1 macaque monkey sleep disruption psychosis aging

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Genetically modified non-human primate models for research on neurodegenerative diseases

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Zoological Research 2024年第2期45卷 263-274页

作者： Ming-Tian Pan Han Zhang Xiao-Jiang Li Xiang-Yu Guo Guangdong Key Laboratory of Non-human Primate Research Guangdong-Hongkong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong 510632China

Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical *** the population ages,NDs are imposing a huge burden on public health systems and affected *** models are important tools for preclinical investigations to understand disease pathogenesis and test potential *** numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation *** World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to *** is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience ***,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel *** review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.

关键词： Neurodegeneration Non-human primate macaque monkey Animal model Gene modification

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*** normalization in monkey primary visual cortex(V1)

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Annals of Eye Science 2019年第1期 190-190页

作者： Alexandre Reynaud Sébastien Roux Sandrine Chemla Frédéric Chavane Robert F.Hess McGill Vision Research Department of Ophthalmology and Visual SciencesMcGill UniversityMontrealQCCanada Institut de Neurosciences de la Timone Centre national de la recherche scientifique(CNRS)MarseilleFrance Aix-Marseilles Université MaseilleFrance UniversitéPaul Sabatier Toulouse III ToulouseFrance

Background:The two images,slightly different,seen by the two eyes allow the brain to build a 3D representation of the *** signals enter the primary visual cortex through layer 4,where they are segregated and organized in ocular dominance *** are later combined in upper *** order to study the integration of the information coming from the two eyes at this mesoscopical scale in V1,we use optical imaging in anaesthetized macaque ***:Ocular dominance maps have been obtained with intrinsic optical *** interactions have then been studied with voltage-sensitive dye imaging(VSDI)with a frequency-tagging *** stimuli with different contrasts were respectively presented at 6 and 10 Hz to the two eyes,independently or simultaneously with a passive 3D *** analysis thus allowed to identify each eye’s contribution to the ***:We observed that V1 population activity generated by one eye stimulation is suppressed when the other eye is stimulated *** integration of monocular signals at the population level can be accurately modeled with an interocular normalization ***:This approach and this model confirm V1 implication in combining the signals coming from the two *** mechanisms underlying this interocular normalization,through local,feedforward,feedback or long-range connections,are still to be determined.

关键词： Binocular vision macaque monkey normalisation optical imaging

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