Pygmy lorises are arboreal primates primarily found in forest environments across Southeast Asia(Nekaris 2014).Theyhave a diverse diet,including plant secretions,nectar,fruits,invertebrates,tree bark,and bird eggs.All...Pygmy lorises are arboreal primates primarily found in forest environments across Southeast Asia(Nekaris 2014).Theyhave a diverse diet,including plant secretions,nectar,fruits,invertebrates,tree bark,and bird eggs.All 9 known speciesof pygmy lorises are listed as globally endangered species(Nekaris 2014).Pygmy lorises exhibit a range of unique phenotypic characteristics rarely seen among primates.展开更多
Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied fo...Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.展开更多
Demyelination and remyelination play key roles in spinal cord injury(SCI),affecting the recovery of motor and sensory functions.Research in rodent models is extensive,but the study of these processes in non-human prim...Demyelination and remyelination play key roles in spinal cord injury(SCI),affecting the recovery of motor and sensory functions.Research in rodent models is extensive,but the study of these processes in non-human primates is limited.Therefore,our goal was to thoroughly study the histological features of demyelination and remyelination after contusion injury of the cervical spinal cord in Macaca fascicularis.In a previous study,we created an SCI model in M.fascicularis by controlling the contusion displacement.We used Eriochrome Cyanine staining,immunohistochemical analysis,and toluidine blue staining to evaluate demyelination and remyelination.The results showed demyelination ipsilateral to the injury epicenter both rostrally and caudally,the former mainly impacting sensory pathways,while the latter primarily affected motor pathways.Toluidine blue staining showed myelin loss and axonal distension at the injury site.Schwann cell-derived myelin sheaths were only found at the center,while thinner myelin sheaths from oligodendrocytes were seen at the center and surrounding areas.Our study showed that long-lasting demyelination occurs in the spinal cord of M.fascicularis after SCI,with oligodendrocytes and Schwann cells playing a significant role in myelin sheath formation at the injury site.展开更多
Alzheimer's disease(AD),the most prevalent form of dementia,disproportionately affects the elderly population.While aging is widely recognized as a major risk factor for AD,the precise mechanisms by which aging co...Alzheimer's disease(AD),the most prevalent form of dementia,disproportionately affects the elderly population.While aging is widely recognized as a major risk factor for AD,the precise mechanisms by which aging contributes to the pathogenesis of AD remain poorly understood.In our previous work,the neuropathological changes in the brains of aged cynomolgus monkeys(≥18 years old)following parenchymal cerebral injection of amyloid-β oligomers(AβOs)have been characterized.Here,we extend our investigation to middle-aged cynomolgus monkeys(≤15 years old)to establish an AD model.Surprisingly,immunohistochemical analysis reveals no detectable AD-related pathology in the brains of middle-aged monkeys,even after AβOs injection.In a comprehensive pathological analysis of 38 monkeys,we observe that the amyloid-β(Aβ)burden increases significantly with advancing age.Notably,the density of Aβ plaques is markedly higher in the ventral regions compared with the dorsal regions of aged monkey brains.Furthermore,we demonstrate that tau phosphorylation coincides with the accumulation of extensive Aβplaques and exhibits a positive correlation with Aβ burden in aged monkeys.Collectively,these findings underscore the critical role of the aged brain in providing the necessary conditions for AβO-induced AD pathologies in cynomolgus monkeys.展开更多
Disaster risk reduction,an essential function of protected areas(PAs),has been generally overlooked in PA design.Using primates as a model,we designed a disaster risk index(DRI)to measure the disaster sensitivity of p...Disaster risk reduction,an essential function of protected areas(PAs),has been generally overlooked in PA design.Using primates as a model,we designed a disaster risk index(DRI)to measure the disaster sensitivity of primate species.High-conservation-need(HCN)areas were identified by both their richness and number of threatened primate species.We also constructed high-disaster-risk(HDR)areas and climate-sensitive(CS)areas based on a disaster risk assessment and temperature change under climate change.We overlaid HCN and HDR areas to obtain HDR-HCN areas.We defined species conservation targets as the percent of each species’range that should be effectively conserved using“Zonation”.Landslides had the highest DRI(1.43±0.88),but have been overlooked in previous studies.PA coverage in HDR-HCN(30%)areas was similar to that in HCN areas(28%),indicating that current PA design fails to account for disaster risk reduction.About 50%of the HDR-HCN areas overlapped with CS areas.Presently,43%of primate species meet their conservation targets.Fifty-seven of primate species would meet their conservation targets and 67%of primates could benefit from PA expansion if HDR-HCN areas are fully incorporated into PAs.Increasing PA coverage in HDR-HCN areas is essential to achieving both primate conservation and disaster risk reduction.The study calls for integrating disaster risk reduction into PA design guidelines,particularly in regions like the western Amazon,and recommends flexible conservation approaches in other areas.展开更多
Sleeping site selection is essential for understanding primate behavioral ecology and survival.Identifying where species sleep helps determine priority areas and critical resources for targeted conservation efforts.Ho...Sleeping site selection is essential for understanding primate behavioral ecology and survival.Identifying where species sleep helps determine priority areas and critical resources for targeted conservation efforts.However,observing sleeping sites at night is challenging,especially for species sensitive to human disturbance.Thermal infrared imaging(TIR)with drones is increasingly used for detecting and counting primates,yet it has not been utilized to investigate ecological strategies.This study investigates the sleeping site selection of the Critically Endangered black-shanked douc langur(Pygathrix nigripes)in Cát Tiên National Park,Vietnam.Our aim is to assess the feasibility of using a TIR drone to test sleeping site selection strategies in non-nesting primates,specifically examining hypotheses related to predation avoidance and food proximity.Between January and April 2023,we conducted 120 drone flights along 22 transects(~1-km long)and identified 114 sleeping sites via thermal imaging.We established 116 forest structure plots along 29 transects in non-selected sites and 65 plots within douc langur sleeping sites.Our observations reveal that douc langurs selected tall and large trees that may provide protection against predators.Additionally,they selected sleeping sites with increased access to food,such as Afzelia xylocarpa,which serves as a preferred food source during the dry season.These results highlight the effective use of TIR drones for studying douc langur sleeping site selection with minimal disturbance.Besides offering valuable insights into habitat selection and behavioral ecology for conservation,TIR drones hold great promise for the noninvasive and long-term monitoring of large-bodied arboreal species.展开更多
Selective regulation of gene expression across distinct brain regions is crucial for establishing and maintaining subdivision identities.DNA methylation,a key regulator of gene transcription,modulates transcriptional ...Selective regulation of gene expression across distinct brain regions is crucial for establishing and maintaining subdivision identities.DNA methylation,a key regulator of gene transcription,modulates transcriptional activity through the conversion of 5-methylcytosine(5mC)to 5-hydroxymethylcytosine(5hmC).While DNA methylation is hypothesized to play an essential role in shaping brain identity by influencing gene expression patterns,its direct contribution,especially in primates,remains largely unexplored.This study examined DNA methylation landscapes and transcriptional profiles across four brain regions,including the cortex,cerebellum,striatum,and hippocampus,using samples from 12 rhesus monkeys.The cerebellum exhibited distinct epigenetic and transcriptional signatures,with differentially methylated regions(DMRs)significantly enriched in metabolic pathways.Notably,genes harboring clustered differentially hydroxymethylated regions(DhMRs)overlapped with those implicated in schizophrenia.Moreover,5mC located1 kb upstream of the ATG start codon was correlated with gene expression and exhibited region-specific associations with 5hmC.These findings provide insights into the coordinated regulation of cerebellum-specific 5mC and5hmC,highlighting their potential roles in defining cerebellar identity and contributing to neuropsychiatric diseases.展开更多
Dear Editor,Traumatic optic neuropathy(TON)is a severe vision-threatening condition,with an incidence rate ranging from 0.7% to 2.5%[1].The limited regenerative capacity of the optic nerve and the challenges of nerve ...Dear Editor,Traumatic optic neuropathy(TON)is a severe vision-threatening condition,with an incidence rate ranging from 0.7% to 2.5%[1].The limited regenerative capacity of the optic nerve and the challenges of nerve transplantation result in substantial and irreversible visual loss in patients with TON.展开更多
Cancer is the second leading disease causing human death.Pre-clinical in vivo studies are essential for translating in vitro laboratory research results into the clinic.Rodents,including the mouse and rat,have been wi...Cancer is the second leading disease causing human death.Pre-clinical in vivo studies are essential for translating in vitro laboratory research results into the clinic.Rodents,including the mouse and rat,have been widely used for pre-clinical studies due to their small size,clear genetic backgrounds,rapid propagation,and mature transgenic technologies.However,because rodents are evolutionarily distinct from humans,many pre-clinical research results using rodent models cannot be reproduced in the clinic.Non-human primates（NHPs） may be better animal models than rodents for human cancer research because NHPs and humans share greater similarity in regards to their genetic evolution,immune system,physiology and metabolism.This article reviews the latest progress of cancer research in NHPs by focusing on the carcinogenesis of different NHPs induced by chemical and biological carcinogens.Finally,future research directions for the use of NHPs in cancer research are discussed.展开更多
Non-human primates （NHPs） are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biom...Non-human primates （NHPs） are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China＇s growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China＇s life sciences and pharmaceutical industry, and enhance China＇s position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective to better utilize NHP resources and further foster NHP research in China.展开更多
In order to understand the fundamental questions of the biology of life and to duplicate the pathogenesis of human diseases, animal models using different experimental animals, such as rodents, Drosophila, Caenorhabdi...In order to understand the fundamental questions of the biology of life and to duplicate the pathogenesis of human diseases, animal models using different experimental animals, such as rodents, Drosophila, Caenorhabditis elegans, and zebrafish, have been established and used widely for many decades. The controllability of environmental conditions, the high reproducibility, the ease of scale and the comparability of results, as well as the ability to use different standards for ethical protocols, all make an animal model the ideal tool for carrying out studies on human diseases and the development of novel pharmaceuticals and new therapies （Xue et al., 2014）. An ideal animal model should reflect the complete spectra of a specific human disease, with similar features on the following key issues： （1） genetic basis; （2） anatomy and physiology; （3） pathological response（s） and underlying mechanism（s）; （4） phenotypic endpoints as clinical studies; （5） responsiveness to known drugs with clinical efficacy; and （6） prediction of clinical efficacy （McGonigle and Ruggeri, 2014）.展开更多
We emphasize the importance of studying the primate brain in cognitive neuroscience and suggest a new mind-set in primate experimentation within the boundaries of animal welfare regulations.Specifically,we list the ad...We emphasize the importance of studying the primate brain in cognitive neuroscience and suggest a new mind-set in primate experimentation within the boundaries of animal welfare regulations.Specifically,we list the advantages of investigating both genes and neural mechanisms and processes in the emergence of behavioral and cognitive functions,and propose the establishment of an open field of primate research.The latter may be conducted by implementing and harmonizing experimental practices with ethical guidelines that regulate(1)management of natural parks with free-moving populations of target nonhuman primates,(2)establishment of indoor-outdoor labs for both system genetics and neuroscience investigations,and(3)hotel space and technologies which remotely collect and dislocate information regarding primates geographically located elsewhere.展开更多
Human functional MRI studies in acute and various chronic pain conditions have revolutionized how we view pain, and have led to a new theory that complex multi-dimensional pain experience （sensory-discriminative, aff...Human functional MRI studies in acute and various chronic pain conditions have revolutionized how we view pain, and have led to a new theory that complex multi-dimensional pain experience （sensory-discriminative, affective/motivational, and cognitive） is represented by concurrent activity in widely-distributed brain regions （termed a network or pain matrix）. Despite these break- through discoveries, the specific functions proposed for these regions remain elusive, because detailed electrophys- iological characterizations of these regions in the primate brain are lacking. To fill in this knowledge gap, we have studied the cortical areas around the central and lateral sulci of the non-human primate brain with combined submillimeter resolution functional imaging （optical imaging and fMRI） and intracranial electrophysiological recording. In this mini-review, I summarize and present data showing that the cortical circuitry engaged in nociceptive processing is much more complex than previously recognized. Electrophysiological evidence supports the engage- ment of a distinct nociceptive-processing network within SI （i.e., areas 3a, 3b, 1 and 2）, SII, and other areas along the lateral sulcus. Deafferentation caused by spinal cord injury profoundly alters the relationships between fMRI and electrophysiological signals. This finding has significant implications for using fMRI to study chronic pain conditions involving deafferentation in humans.展开更多
The central nervous system is known to have limited regenerative capacity.Not only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of ef...The central nervous system is known to have limited regenerative capacity.Not only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of effective and safe therapeutic options for such patients.Despite the high prevalence of stroke and spinal cord injury in the general population,these conditions remain incurable and place a heavy burden on patients’families and on society more broadly.Neuroregeneration and neural engineering are diverse biomedical fields that attempt reparative treatments,utilizing stem cells-based strategies,biologically active molecules,nanotechnology,exosomes and highly tunable biodegradable systems(e.g.,certain hydrogels).Although there are studies demonstrating promising preclinical results,safe clinical translation has not yet been accomplished.A key gap in clinical translation is the absence of an ideal animal or ex vivo model that can perfectly simulate the human microenvironment,and also correspond to all the complex pathophysiological and neuroanatomical factors that affect functional outcomes in humans after central nervous system injury.Such an ideal model does not currently exist,but it seems that the nonhuman primate model is uniquely qualified for this role,given its close resemblance to humans.This review considers some regenerative therapies for central nervous system repair that hold promise for future clinical translation.In addition,it attempts to uncover some of the main reasons why clinical translation might fail without the implementation of nonhuman primate models in the research pipeline.展开更多
The ongoing coronavirus disease 2019(COVID-19)pandemic caused more than 96 million infections and over 2 million deaths worldwide so far.However,there is no approved vaccine available for severe acute respiratory synd...The ongoing coronavirus disease 2019(COVID-19)pandemic caused more than 96 million infections and over 2 million deaths worldwide so far.However,there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the disease causative agent.Vaccine is the most effective approach to eradicate a pathogen.The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations.Here we evaluated the safety,immunogenicity,and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates.Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates,and subsequently provided partial(in low dose)or full(in high dose)protection of challenge in the tested animals.In addition,passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice.These results warranted positive outcomes in future clinical trials in humans.展开更多
Stem cell therapy (SCT) for Parkinson’s disease (PD) has received considerable attention in recent years. Non-human primate (NHP) models of PD have played an instrumental role in the safety and efficacy of emerging P...Stem cell therapy (SCT) for Parkinson’s disease (PD) has received considerable attention in recent years. Non-human primate (NHP) models of PD have played an instrumental role in the safety and efficacy of emerging PD therapies and facilitated the translation of initiatives for human patients. NHP models of PD include primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism, who are responsive to dopamine replacement therapies, similar to human PD patients. Extensive research in SCT has been conducted to better treat the progressive dopaminergic neurodegeneration that underlies PD. For effective application of SCT in PD, however, a number of basic parameters still need to be tested and optimized in NHP models, including preparation and storage of cells for engraftment, methods of transplantation, choice of target sites, and timelines for recovery. In this review, we discuss the current status of NHP models of PD in stem cell research. We also analyze the advances and remaining challenges for successful clinical translation of SCT for this persistent disease.展开更多
In the past three years, RNA-guided Cas9 nuclease from the microbial clustered regularly interspaced short palindromic repeats （CRISPR） adaptive immune system has been used to facilitate efficient genome editing in ...In the past three years, RNA-guided Cas9 nuclease from the microbial clustered regularly interspaced short palindromic repeats （CRISPR） adaptive immune system has been used to facilitate efficient genome editing in many model and non-model animals. However, its application in nonhuman primates is still at the early stage, though in view of the similarities in anatomy, physiology, behavior and genetics, closely related nonhuman primates serve as optimal models for human biology and disease studies. In this review, we summarize the current proceedings of gene editing using CRISPR/Cas9 in nonhuman primates.展开更多
Nonhuman primates （NHPs） provide powerful experimental models to study human development, cognitive functions and disturbances as well as complex behavior, because of their genetic and physiological similarities to ...Nonhuman primates （NHPs） provide powerful experimental models to study human development, cognitive functions and disturbances as well as complex behavior, because of their genetic and physiological similarities to humans. Therefore, NHPs are appropriate models for the study of human diseases, such as neurodegenerative diseases including Parkinson＇s, Alzheimer＇s and Huntington＇s diseases, which occur as a result of genetic mutations. However, such diseases afflicting humans do not occur naturally in NHPs. So transgenic NHPs need to be established to understand the etiology of disease pathology and pathogenesis. Compared to rodent genetic models, the generation of transgenic NHPs for human diseases is inefficient, and only a transgenic monkey model for Huntington＇s disease has been reported. This review focuses on potential approaches and contributing factors for generating transgenic NHPs to study human diseases.展开更多
China is one of the most dynamic countries of the world and it shelters some amazing levels of biodiversity, including some very special primate species. However, primarily as a result of forest loss, most of which oc...China is one of the most dynamic countries of the world and it shelters some amazing levels of biodiversity, including some very special primate species. However, primarily as a result of forest loss, most of which occurred in historical times, approximately 70% of China＇s primate species have less than 3 000 individuals. Here I evaluate one road for future conservation/development that could produce very positive gains for China＇s primates; namely forest restoration. I argue that for a large scale restoration project to be possible two conditions must be met; the right societal conditions must exist and the right knowledge must be in hand. This evaluation suggests that the restoration of native forest to support many of China＇s primates holds great potential to advance conservation goals and to promote primate population recovery.展开更多
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(...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 settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While 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 gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This 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.展开更多
基金supported by the Shaanxi FundamentalScience Research Project for Chemistry&Biology(grant no.22JHQ049)Basic Research Program of Natural Sciencesof Shaanxi Province(2019JM-339).
文摘Pygmy lorises are arboreal primates primarily found in forest environments across Southeast Asia(Nekaris 2014).Theyhave a diverse diet,including plant secretions,nectar,fruits,invertebrates,tree bark,and bird eggs.All 9 known speciesof pygmy lorises are listed as globally endangered species(Nekaris 2014).Pygmy lorises exhibit a range of unique phenotypic characteristics rarely seen among primates.
文摘Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.
基金supported by the National Natural Science Foundation of China(81972064)the Guangdong Basic and Applied Basic Research Foundation(2021A1515111117,2020A1515011415).
文摘Demyelination and remyelination play key roles in spinal cord injury(SCI),affecting the recovery of motor and sensory functions.Research in rodent models is extensive,but the study of these processes in non-human primates is limited.Therefore,our goal was to thoroughly study the histological features of demyelination and remyelination after contusion injury of the cervical spinal cord in Macaca fascicularis.In a previous study,we created an SCI model in M.fascicularis by controlling the contusion displacement.We used Eriochrome Cyanine staining,immunohistochemical analysis,and toluidine blue staining to evaluate demyelination and remyelination.The results showed demyelination ipsilateral to the injury epicenter both rostrally and caudally,the former mainly impacting sensory pathways,while the latter primarily affected motor pathways.Toluidine blue staining showed myelin loss and axonal distension at the injury site.Schwann cell-derived myelin sheaths were only found at the center,while thinner myelin sheaths from oligodendrocytes were seen at the center and surrounding areas.Our study showed that long-lasting demyelination occurs in the spinal cord of M.fascicularis after SCI,with oligodendrocytes and Schwann cells playing a significant role in myelin sheath formation at the injury site.
基金supported in part by the National Key Basic Research and Development Program of China(2019YFA0801402,2018YFA0107200,2018YFA0801402,2018YFA0800100)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16020501 and XDA16020404)the National Natural Science Foundation of China(32130030,31900454,32470866,32471010,32100800)。
文摘Alzheimer's disease(AD),the most prevalent form of dementia,disproportionately affects the elderly population.While aging is widely recognized as a major risk factor for AD,the precise mechanisms by which aging contributes to the pathogenesis of AD remain poorly understood.In our previous work,the neuropathological changes in the brains of aged cynomolgus monkeys(≥18 years old)following parenchymal cerebral injection of amyloid-β oligomers(AβOs)have been characterized.Here,we extend our investigation to middle-aged cynomolgus monkeys(≤15 years old)to establish an AD model.Surprisingly,immunohistochemical analysis reveals no detectable AD-related pathology in the brains of middle-aged monkeys,even after AβOs injection.In a comprehensive pathological analysis of 38 monkeys,we observe that the amyloid-β(Aβ)burden increases significantly with advancing age.Notably,the density of Aβ plaques is markedly higher in the ventral regions compared with the dorsal regions of aged monkey brains.Furthermore,we demonstrate that tau phosphorylation coincides with the accumulation of extensive Aβplaques and exhibits a positive correlation with Aβ burden in aged monkeys.Collectively,these findings underscore the critical role of the aged brain in providing the necessary conditions for AβO-induced AD pathologies in cynomolgus monkeys.
基金supported by the Ministry of Science and Technology of China(Grant No.2022YFF1301500)the National Natural Science Foun-dation of China(Grants No.32000352,32171485,and 32371741)+1 种基金the Natural Science Foundation of Guangdong Province(Grant No.2021A1515010968)Fundamental Research Funds for the Central Universities,Sun Yat-sen University(Grant No.23lgzy002).
文摘Disaster risk reduction,an essential function of protected areas(PAs),has been generally overlooked in PA design.Using primates as a model,we designed a disaster risk index(DRI)to measure the disaster sensitivity of primate species.High-conservation-need(HCN)areas were identified by both their richness and number of threatened primate species.We also constructed high-disaster-risk(HDR)areas and climate-sensitive(CS)areas based on a disaster risk assessment and temperature change under climate change.We overlaid HCN and HDR areas to obtain HDR-HCN areas.We defined species conservation targets as the percent of each species’range that should be effectively conserved using“Zonation”.Landslides had the highest DRI(1.43±0.88),but have been overlooked in previous studies.PA coverage in HDR-HCN(30%)areas was similar to that in HCN areas(28%),indicating that current PA design fails to account for disaster risk reduction.About 50%of the HDR-HCN areas overlapped with CS areas.Presently,43%of primate species meet their conservation targets.Fifty-seven of primate species would meet their conservation targets and 67%of primates could benefit from PA expansion if HDR-HCN areas are fully incorporated into PAs.Increasing PA coverage in HDR-HCN areas is essential to achieving both primate conservation and disaster risk reduction.The study calls for integrating disaster risk reduction into PA design guidelines,particularly in regions like the western Amazon,and recommends flexible conservation approaches in other areas.
基金financial support of the Belgian National Fund for Scientific Research(FNRS)the Duesberg Foundation,and the University of Liège.
文摘Sleeping site selection is essential for understanding primate behavioral ecology and survival.Identifying where species sleep helps determine priority areas and critical resources for targeted conservation efforts.However,observing sleeping sites at night is challenging,especially for species sensitive to human disturbance.Thermal infrared imaging(TIR)with drones is increasingly used for detecting and counting primates,yet it has not been utilized to investigate ecological strategies.This study investigates the sleeping site selection of the Critically Endangered black-shanked douc langur(Pygathrix nigripes)in Cát Tiên National Park,Vietnam.Our aim is to assess the feasibility of using a TIR drone to test sleeping site selection strategies in non-nesting primates,specifically examining hypotheses related to predation avoidance and food proximity.Between January and April 2023,we conducted 120 drone flights along 22 transects(~1-km long)and identified 114 sleeping sites via thermal imaging.We established 116 forest structure plots along 29 transects in non-selected sites and 65 plots within douc langur sleeping sites.Our observations reveal that douc langurs selected tall and large trees that may provide protection against predators.Additionally,they selected sleeping sites with increased access to food,such as Afzelia xylocarpa,which serves as a preferred food source during the dry season.These results highlight the effective use of TIR drones for studying douc langur sleeping site selection with minimal disturbance.Besides offering valuable insights into habitat selection and behavioral ecology for conservation,TIR drones hold great promise for the noninvasive and long-term monitoring of large-bodied arboreal species.
基金supported by the Natural Science Foundation of Guangdong Province(2022A1515010689)National Natural Science Foundation of China(82394422,82371874,82071421,82271902)Department of Science and Technology of Guangdong Province(2021ZT09Y007,2020B121201006)。
文摘Selective regulation of gene expression across distinct brain regions is crucial for establishing and maintaining subdivision identities.DNA methylation,a key regulator of gene transcription,modulates transcriptional activity through the conversion of 5-methylcytosine(5mC)to 5-hydroxymethylcytosine(5hmC).While DNA methylation is hypothesized to play an essential role in shaping brain identity by influencing gene expression patterns,its direct contribution,especially in primates,remains largely unexplored.This study examined DNA methylation landscapes and transcriptional profiles across four brain regions,including the cortex,cerebellum,striatum,and hippocampus,using samples from 12 rhesus monkeys.The cerebellum exhibited distinct epigenetic and transcriptional signatures,with differentially methylated regions(DMRs)significantly enriched in metabolic pathways.Notably,genes harboring clustered differentially hydroxymethylated regions(DhMRs)overlapped with those implicated in schizophrenia.Moreover,5mC located1 kb upstream of the ATG start codon was correlated with gene expression and exhibited region-specific associations with 5hmC.These findings provide insights into the coordinated regulation of cerebellum-specific 5mC and5hmC,highlighting their potential roles in defining cerebellar identity and contributing to neuropsychiatric diseases.
基金supported by Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology(20200730009)the National Natural Science Foundation of China(81870656)the Natural Science Foundation of Guangdong Province of China(2017A030313610 and 2023A1515012397).
文摘Dear Editor,Traumatic optic neuropathy(TON)is a severe vision-threatening condition,with an incidence rate ranging from 0.7% to 2.5%[1].The limited regenerative capacity of the optic nerve and the challenges of nerve transplantation result in substantial and irreversible visual loss in patients with TON.
基金supported in part by a grant from Yunnan Province High-Profile Talent Project 2010CI114grants from Chinese Academy of Sciences(Basic frontier project,KSCX2-EW-J-23)~~
文摘Cancer is the second leading disease causing human death.Pre-clinical in vivo studies are essential for translating in vitro laboratory research results into the clinic.Rodents,including the mouse and rat,have been widely used for pre-clinical studies due to their small size,clear genetic backgrounds,rapid propagation,and mature transgenic technologies.However,because rodents are evolutionarily distinct from humans,many pre-clinical research results using rodent models cannot be reproduced in the clinic.Non-human primates（NHPs） may be better animal models than rodents for human cancer research because NHPs and humans share greater similarity in regards to their genetic evolution,immune system,physiology and metabolism.This article reviews the latest progress of cancer research in NHPs by focusing on the carcinogenesis of different NHPs induced by chemical and biological carcinogens.Finally,future research directions for the use of NHPs in cancer research are discussed.
基金supported by the National Natural Science Foundation of China(81172876,81273251,U1202228,81471620)the National Special Science Research Program of China(2012CBA01305)+1 种基金the National Science and Technology Major Project(2013ZX10001-002,2012ZX10001-007)the Knowledge Innovation Program of CAS(KSCX2-EW-R-13,KJZD-EW-L10-02)
文摘Non-human primates （NHPs） are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China＇s growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China＇s life sciences and pharmaceutical industry, and enhance China＇s position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective to better utilize NHP resources and further foster NHP research in China.
文摘In order to understand the fundamental questions of the biology of life and to duplicate the pathogenesis of human diseases, animal models using different experimental animals, such as rodents, Drosophila, Caenorhabditis elegans, and zebrafish, have been established and used widely for many decades. The controllability of environmental conditions, the high reproducibility, the ease of scale and the comparability of results, as well as the ability to use different standards for ethical protocols, all make an animal model the ideal tool for carrying out studies on human diseases and the development of novel pharmaceuticals and new therapies （Xue et al., 2014）. An ideal animal model should reflect the complete spectra of a specific human disease, with similar features on the following key issues： （1） genetic basis; （2） anatomy and physiology; （3） pathological response（s） and underlying mechanism（s）; （4） phenotypic endpoints as clinical studies; （5） responsiveness to known drugs with clinical efficacy; and （6） prediction of clinical efficacy （McGonigle and Ruggeri, 2014）.
文摘We emphasize the importance of studying the primate brain in cognitive neuroscience and suggest a new mind-set in primate experimentation within the boundaries of animal welfare regulations.Specifically,we list the advantages of investigating both genes and neural mechanisms and processes in the emergence of behavioral and cognitive functions,and propose the establishment of an open field of primate research.The latter may be conducted by implementing and harmonizing experimental practices with ethical guidelines that regulate(1)management of natural parks with free-moving populations of target nonhuman primates,(2)establishment of indoor-outdoor labs for both system genetics and neuroscience investigations,and(3)hotel space and technologies which remotely collect and dislocate information regarding primates geographically located elsewhere.
基金supported by NIH Grant R01 NS069909an imaging track Grant from the Dana Foundation
文摘Human functional MRI studies in acute and various chronic pain conditions have revolutionized how we view pain, and have led to a new theory that complex multi-dimensional pain experience （sensory-discriminative, affective/motivational, and cognitive） is represented by concurrent activity in widely-distributed brain regions （termed a network or pain matrix）. Despite these break- through discoveries, the specific functions proposed for these regions remain elusive, because detailed electrophys- iological characterizations of these regions in the primate brain are lacking. To fill in this knowledge gap, we have studied the cortical areas around the central and lateral sulci of the non-human primate brain with combined submillimeter resolution functional imaging （optical imaging and fMRI） and intracranial electrophysiological recording. In this mini-review, I summarize and present data showing that the cortical circuitry engaged in nociceptive processing is much more complex than previously recognized. Electrophysiological evidence supports the engage- ment of a distinct nociceptive-processing network within SI （i.e., areas 3a, 3b, 1 and 2）, SII, and other areas along the lateral sulcus. Deafferentation caused by spinal cord injury profoundly alters the relationships between fMRI and electrophysiological signals. This finding has significant implications for using fMRI to study chronic pain conditions involving deafferentation in humans.
基金supported by Onassis Foundation(to MT)the National Center for Complementary and Integrative Health(NCCIH),No.R21AT008865(to NM)National Institute of Aging(NIA)/National Institute of Mental Health(NIMH),No.R01AG042512(to NM)
文摘The central nervous system is known to have limited regenerative capacity.Not only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of effective and safe therapeutic options for such patients.Despite the high prevalence of stroke and spinal cord injury in the general population,these conditions remain incurable and place a heavy burden on patients’families and on society more broadly.Neuroregeneration and neural engineering are diverse biomedical fields that attempt reparative treatments,utilizing stem cells-based strategies,biologically active molecules,nanotechnology,exosomes and highly tunable biodegradable systems(e.g.,certain hydrogels).Although there are studies demonstrating promising preclinical results,safe clinical translation has not yet been accomplished.A key gap in clinical translation is the absence of an ideal animal or ex vivo model that can perfectly simulate the human microenvironment,and also correspond to all the complex pathophysiological and neuroanatomical factors that affect functional outcomes in humans after central nervous system injury.Such an ideal model does not currently exist,but it seems that the nonhuman primate model is uniquely qualified for this role,given its close resemblance to humans.This review considers some regenerative therapies for central nervous system repair that hold promise for future clinical translation.In addition,it attempts to uncover some of the main reasons why clinical translation might fail without the implementation of nonhuman primate models in the research pipeline.
基金supported by the National Key R&D Program of China(2020YFC0842000 to Z.M.Yuan and 2020YFC0842100 to C.Shan)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29010101 to Z.L.Shi)+1 种基金the China Natural Science Foundation(82041013 to P.Zhou)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(CAS)(2019328 to X.L.Yang)。
文摘The ongoing coronavirus disease 2019(COVID-19)pandemic caused more than 96 million infections and over 2 million deaths worldwide so far.However,there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the disease causative agent.Vaccine is the most effective approach to eradicate a pathogen.The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations.Here we evaluated the safety,immunogenicity,and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates.Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates,and subsequently provided partial(in low dose)or full(in high dose)protection of challenge in the tested animals.In addition,passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice.These results warranted positive outcomes in future clinical trials in humans.
基金supported by the National Key R&D Program of China(2016YFA0101401)
文摘Stem cell therapy (SCT) for Parkinson’s disease (PD) has received considerable attention in recent years. Non-human primate (NHP) models of PD have played an instrumental role in the safety and efficacy of emerging PD therapies and facilitated the translation of initiatives for human patients. NHP models of PD include primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism, who are responsive to dopamine replacement therapies, similar to human PD patients. Extensive research in SCT has been conducted to better treat the progressive dopaminergic neurodegeneration that underlies PD. For effective application of SCT in PD, however, a number of basic parameters still need to be tested and optimized in NHP models, including preparation and storage of cells for engraftment, methods of transplantation, choice of target sites, and timelines for recovery. In this review, we discuss the current status of NHP models of PD in stem cell research. We also analyze the advances and remaining challenges for successful clinical translation of SCT for this persistent disease.
基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13010000)the National Natural Science Foundation of China(31130051)
文摘In the past three years, RNA-guided Cas9 nuclease from the microbial clustered regularly interspaced short palindromic repeats （CRISPR） adaptive immune system has been used to facilitate efficient genome editing in many model and non-model animals. However, its application in nonhuman primates is still at the early stage, though in view of the similarities in anatomy, physiology, behavior and genetics, closely related nonhuman primates serve as optimal models for human biology and disease studies. In this review, we summarize the current proceedings of gene editing using CRISPR/Cas9 in nonhuman primates.
基金supported by the grants from the Major State Basic Development Program(No. 2012CBA01300)the National High Technology Research and Development Program(No.2012AA020701)+1 种基金the National Science and Technology Major Project(No.2009ZX09501- 028)the Social Science and Technology Development Program of Yunnan Province(No.2007GH)
文摘Nonhuman primates （NHPs） provide powerful experimental models to study human development, cognitive functions and disturbances as well as complex behavior, because of their genetic and physiological similarities to humans. Therefore, NHPs are appropriate models for the study of human diseases, such as neurodegenerative diseases including Parkinson＇s, Alzheimer＇s and Huntington＇s diseases, which occur as a result of genetic mutations. However, such diseases afflicting humans do not occur naturally in NHPs. So transgenic NHPs need to be established to understand the etiology of disease pathology and pathogenesis. Compared to rodent genetic models, the generation of transgenic NHPs for human diseases is inefficient, and only a transgenic monkey model for Huntington＇s disease has been reported. This review focuses on potential approaches and contributing factors for generating transgenic NHPs to study human diseases.
基金Supported by the Canada Research Chairs Programthe Natural Science and Engineering Research Council of CanadaKyoto University
文摘China is one of the most dynamic countries of the world and it shelters some amazing levels of biodiversity, including some very special primate species. However, primarily as a result of forest loss, most of which occurred in historical times, approximately 70% of China＇s primate species have less than 3 000 individuals. Here I evaluate one road for future conservation/development that could produce very positive gains for China＇s primates; namely forest restoration. I argue that for a large scale restoration project to be possible two conditions must be met; the right societal conditions must exist and the right knowledge must be in hand. This evaluation suggests that the restoration of native forest to support many of China＇s primates holds great potential to advance conservation goals and to promote primate population recovery.
基金supported by the National Key Research and Development Program of China (2021YFF0702201)National Natural Science Foundation of China (81873736,31872779,81830032)+2 种基金Guangzhou Key Research Program on Brain Science (202007030008)Department of Science and Technology of Guangdong Province (2021ZT09Y007,2020B121201006,2018B030337001,2021A1515012526)Natural Science Foundation of Guangdong Province (2021A1515012526,2022A1515012651)。
文摘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 settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While 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 gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This 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.
