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Transgenic rhesus monkeys carrying the human MCPH1 gene copies show human-like neoteny of brain development

National Science Review 2019年第3期6卷 480-493页

作者： Lei Shi Xin Luo Jin Jiang Yongchang Chen Cirong Liu Ting Hu Min Li Qiang Lin Yanjiao Li Jun Huang Hong Wang Yuyu Niu Yundi Shi Martin Styner Jianhong Wang Yi Lu Xuejin Sun Hualin Yu Weizhi Ji Bing Su State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Primate Research Center Kunming Institute of Zoology Chinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences Kunming College of Life Science University of Chinese Academy of Sciences Yunnan Key Laboratory of Primate Biomedical Research Institute of Primate Translation Medicine Kunming University of Science and Technology Department of Psychiatry University of North CarolinaChapel Hill Department of Computer Science University of North CarolinaChapel Hill Key Laboratory of Animal Models and Human Disease Mechanisms Kunming Institute of Zoology Chinese Academy of Sciences Department of Medical Imaging the First Affiliated Hospital of Kunming Medical University Department of Minimally Invasive Neurosurgery the First Affiliated Hospital of Kunming Medical University

brain size and cognitive skills are the most dramatically changed traits in humans during evolution and yet the genetic mechanisms underlying these human-specific changes remain elusive. Here, we successfully generated 11 transgenic rhesus monkeys(8 first-generation and 3 second-generation) carrying human copies of MCPH1, an important gene for brain development and brain evolution. brain-image and tissue-section analyses indicated an altered pattern of neural-cell differentiation, resulting in a delayed neuronal maturation and neural-fiber myelination of the transgenic monkeys, similar to the known evolutionary change of developmental delay(neoteny) in humans. Further brain-transcriptome and tissue-section analyses of major developmental stages showed a marked human-like expression delay of neuron differentiation and synaptic-signaling genes, providing a molecular explanation for the observed brain-developmental delay of the transgenic monkeys. More importantly, the transgenic monkeys exhibited better short-term memory and shorter reaction time compared with the wild-type controls in the delayed-matching-to-sample task. The presented data represent the first attempt to experimentally interrogate the genetic basis of human brain origin using a transgenic monkey model and it values the use of non-human primates in understanding unique human traits.

关键词： human evolution brain development MCPH1 transgenic monkey neoteny cognition

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Impact of SARS-CoV-2 infection during pregnancy on postnatal brain development:The potential role of glial cells

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BIOCELL 2022年第12期46卷 2517-2523页

作者： LARISSA DANIELE BOBERMIN LARA SCOPEL MEDEIROS FERNANDA WEBER GIANCARLO TOMAZZONI DE OLIVEIRA LUCÉLIA SANTI WALTER ORLANDO BEYS-DA-SILVA CARLOS-ALBERTO GONÇALVES ANDRÉQUINCOZES-SANTOS Programa de Pós-Graduação emNeurociências Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do SulPorto Alegre90050170Brazil Departamento de Bioquímica Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do SulPorto Alegre90035003Brazil Faculdade de Farmácia Universidade Federal do Rio Grande do SulPorto Alegre90610000Brazil Hospital de Clínicas de Porto Alegre Porto Alegre90035903Brazil Programa de Pós-Graduação emBiologia Celular eMolecular Centro de BiotecnologiaUniversidade Federal do Rio Grande do SulPorto Alegre91501970Brazil Programa de Pós-Graduação em Ciências Biológicas:Bioquímica Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do SulPorto Alegre90035003Brazil

Glial cells are crucial for maintaining central nervous system(CNS)*** actively participate in immune responses,as well as form functional barriers,such as blood-brain barrier(BBB),which restrict the entry of pathogens and inflammatory mediators into the *** general,viral infections during the gestational period can alter the embryonic and fetal environment,and the related inflammatory response may affect neurodevelopment and lead to behavioral dysfunction during later stage of life,as highlighted by our group for Zika virus *** acute respiratory syndrome coronavirus-2(SARS-CoV-2)induces a cytokine storm and,during pregnancy,may be related to a more severe form of the coronavirus disease-19(COVID-19)and also to higher preterm birth ***-CoV-2 can also affect the CNS by inducing neurochemical remodeling in neural cells,which can compromise neuronal plasticity and synaptic ***,the impact of SARS-CoV-2 infection during pregnancy on postnatal CNS,including brain development during childhood and adulthood,remains *** group has recently highlighted the impact of COVID-19 on the expression of molecular markers associated with neuropsychiatric disorders,which are strongly related to the inflammatory ***,based on these relationships,we discussed the impact of SARS-CoV-2 infection either during pregnancy or in critical periods of neurodevelopment as a risk factor for neurological consequences in the offspring later in life,focusing on the potential role of glial ***,it is important to consider future and long-term public health concerns associated with SARS-CoV-2 infection during pregnancy.

关键词： brain development Glial cells Inflammation Pregnancy SARS-CoV-2

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Regulation of neural stem cell by bone morphogenetic protein (BMP) signaling during brain development

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Frontiers in Biology 2010年第5期5卷 380-385页

作者： Yiming SUN Zhiheng XU The Key Laboratory of Molecular and developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

Neurogenesis is the process in which neurons are generated from neural stem/progenitor cells(NSCs/NPCs).It involves the proliferation and neuronal fate speciﬁcation/differentiation of NSCs,as well as migration,maturation and functional integration of the neuronal progeny into neuronal *** exhibit the two essential properties of stem cells:self-renewal and *** to previous dogma that neurogenesis happens only during development,it is generally accepted now that neurogenesis can take place throughout life in mammalian *** raises a new therapeutic potential of applying stem cell therapy for stroke,neurodegenerative diseases and other ***,the maintenance and differentiation of NSCs/NPCs are tightly controlled by the extremely intricate molecular *** the underlying mechanisms that drive the differentiation,migration and maturation of speciﬁc neuronal lineages for use in regenerative medicine is,therefore,crucial for the application of stem cell for clinical therapy as well as for providing insight into the mechanisms of human ***,we focus on the role of bone morphogenetic protein(BMP)signaling in NSCs during mammalian brain development.

关键词： Bone morphogenetic protein(BMP) neural stem cell neural progenitor cell neural differentiation neuronal migration brain development collapsing response mediator protein 2(CRMP2)

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Tetrabromobisphenol A exerts thyroid disrupting effects but has little overt impact on postnatal brain development and neurobehaviors in mice

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Journal of Environmental Sciences 2024年第8期142卷 1-10页

作者： Shilin Song Yuanyuan Li Lin Lv Mengqi Dong Zhanfen Qin State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China College of Resources and Environment University of Chinese Academy of SciencesBeijing 100049China School of Environment Tsinghua UniversityBeijing 100084China

Tetrabromobisphenol A(TBBPA)is a widely used brominated flame *** is evidence showing that TBBPA can exert thyroid disrupting effects in mammals,but different results were also reported,along with inconsistent reports regarding its ***,we investigated thyroid disrupting effects and neurotoxicity of TBBPA(5,50,500μg/(kg·day))to male mice following maternal and direct exposure through drinking water,with the antithyroid drug propylthiouracil(PTU)as the positive *** postnatal day(PND)15,we expectedly observed severe thyroid compensatory hyperplasia and cerebellar developmental retardation in PTU-treated *** highest dose of TBBPA also caused thyroid histological alteration but had no effects on cerebellar development in terms of Purkinje cell morphology and the thickness of the internal granular layer and the molecular layer of the *** puberty and adulthood,the thyroid morphological alterations became more pronounced in the TBBPA-treated animals,accompanied by decreased serum thyroid hormone ***,the 50 and 500μg/(kg·day)TBBPA groups showed a significant decrease in the serum level of serotonin,a neurotransmitter associated with anxiety ***,the highest dose group displayed anxiety-like behaviors in the elevated plus-maze test on PND 35,but this neurobehavioral alteration disappeared on PND ***,no changes in neurobehavioral parameters tested were found in TBBPAtreated animals at puberty and ***,all observations show that TBBPA can exert thyroid disrupting effects but has little overt impact on brain development and neurobehaviors in mice,suggesting that thyroid disruption does not necessarily cause overtly adverse neurodevelopmental outcomes.

关键词： Tetrabromobisphenol A Thyroid disruption brain development Neurobehavior Cerebellum

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development of functional connectome gradients during childhood and adolescence

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Science Bulletin 2022年第10期67卷 1049-1061,M0004页

作者： Yunman Xia Mingrui Xia Jin Liu Xuhong Liao Tianyuan Lei Xinyu Liang Tengda Zhao Ziyi Shi Lianglong Sun Xiaodan Chen Weiwei Men Yanpei Wang Zhiying Pan Jie Luo Siya Peng Menglu Chen Lei Hao Shuping Tan Jia-Hong Gao Shaozheng Qin Gaolang Gong Sha Tao Qi Dong Yong He State Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal UniversityBeijing 100875China Beijing Key Laboratory of brain Imaging and Connectomics Beijing Normal UniversityBeijing 100875China IDG/McGovern Institute for brain Research Beijing Normal UniversityBeijing 100875China School of Systems Science Beijing Normal UniversityBeijing 100875China Center for MRI Research Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100871China Beijing City Key Laboratory for Medical Physics and Engineering Institute of Heavy Ion PhysicsSchool of PhysicsPeking UniversityBeijing 100871China Beijing Huilongguan Hospital Peking University Huilongguan Clinical Medical SchoolBeijing 100096China IDG/McGovern Institute for brain Research Peking UniversityBeijing 100871China Chinese Institute for brain Research Beijing 102206China

Connectome mapping studies have documented a principal primary-to-transmodal gradient in the adult brain network,capturing a functional spectrum that ranges from perception and action to abstract ***,how this gradient pattern develops and whether its development is linked to cognitive growth,topological reorganization,and gene expression profiles remain largely *** longitudinal resting-state functional magnetic resonance imaging data from 305 children(aged 6-14 years),we describe substantial changes in the primary-to-transmodal gradient between childhood and adolescence,including emergence as the principal gradient,expansion of global topography,and focal tuning in primary and default-mode *** gradient changes are mediated by developmental changes in network integration and segregation,and are associated with abstract processing functions such as working memory and expression levels of calcium ion regulated exocytosis and synaptic transmission-related *** findings have implications for understanding connectome maturation principles in normal development and developmental disorders.

关键词： brain development Functional connectome gradient Primary-to-transmodal Working memory Transcriptome

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