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
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
Animal model is an essential tool in the life sciences research, notably in understanding the pathogenesis of the diseases and for further therapeutic intervention success. Rodents have been the most frequently used a...Animal model is an essential tool in the life sciences research, notably in understanding the pathogenesis of the diseases and for further therapeutic intervention success. Rodents have been the most frequently used animals to model human disease since the establishment of gene manipulation technique. However, they remain inadequate to fully mimic the pathophysiology of human brain disease, partially due to huge differences between rodents and humans in terms of anatomy, brain function, and social behaviors. Nonhuman primates are more suitable in translational perspective. Thus, genetically modified animals have been generated to investigate neurologic and psychiatric disorders. The classical transgenesis technique is not efficient in that model; so, viral vector-mediated transgene delivery and the new genome-editing technologies have been promoted. In this review, we summarize some of the technical progress in the generation of an ad hoc animal model of brain diseases by gene delivery and real transgenic nonhuman primate.展开更多
Hippocampal neurogenesis continues throughout the lifespan of adult mammals, but the rates decline dramatically with increasing age. Among the factors that have been shown to affect neurogenesis, aging has been shown ...Hippocampal neurogenesis continues throughout the lifespan of adult mammals, but the rates decline dramatically with increasing age. Among the factors that have been shown to affect neurogenesis, aging has been shown to be one of its most potent regulators in mice. The mechanism for the decline in neurogenesis with age is thought to be related to age-dependent changes in local and systemic neuroendocrinology and neurochemistry, as well as internal changes to precursor cells that result in decreased reactivity to normal stimuli. Since most of the data about neurogenesis and age were established from rodent studies, we sought to study this relationship in nonhuman primates in five previously studied cohorts of bonnet monkeys (Macaca radiata). In the present study, we statistically analyze the relationship of age and hippocampal neurogenesis rates, as measured by the number of DCX expressing cells in the subgranular zone of the dentate gyrus in 71 subjects with ages ranging from 3.5 to 17 years. We observed a non-significant relationship between age and doublecortin for subjects less than nine years old (corresponding to young and full adulthood) but a linear significant decline for subjects 9 years or greater (middle age and senescence). In contrast to previous studies that show neurogenesis to decline linearly throughout the lifespan, this study shows that neurogenesis occurs steadily throughout adulthood and begins to decline in middle age in bonnet macaques.展开更多
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 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.
文摘Animal model is an essential tool in the life sciences research, notably in understanding the pathogenesis of the diseases and for further therapeutic intervention success. Rodents have been the most frequently used animals to model human disease since the establishment of gene manipulation technique. However, they remain inadequate to fully mimic the pathophysiology of human brain disease, partially due to huge differences between rodents and humans in terms of anatomy, brain function, and social behaviors. Nonhuman primates are more suitable in translational perspective. Thus, genetically modified animals have been generated to investigate neurologic and psychiatric disorders. The classical transgenesis technique is not efficient in that model; so, viral vector-mediated transgene delivery and the new genome-editing technologies have been promoted. In this review, we summarize some of the technical progress in the generation of an ad hoc animal model of brain diseases by gene delivery and real transgenic nonhuman primate.
文摘Hippocampal neurogenesis continues throughout the lifespan of adult mammals, but the rates decline dramatically with increasing age. Among the factors that have been shown to affect neurogenesis, aging has been shown to be one of its most potent regulators in mice. The mechanism for the decline in neurogenesis with age is thought to be related to age-dependent changes in local and systemic neuroendocrinology and neurochemistry, as well as internal changes to precursor cells that result in decreased reactivity to normal stimuli. Since most of the data about neurogenesis and age were established from rodent studies, we sought to study this relationship in nonhuman primates in five previously studied cohorts of bonnet monkeys (Macaca radiata). In the present study, we statistically analyze the relationship of age and hippocampal neurogenesis rates, as measured by the number of DCX expressing cells in the subgranular zone of the dentate gyrus in 71 subjects with ages ranging from 3.5 to 17 years. We observed a non-significant relationship between age and doublecortin for subjects less than nine years old (corresponding to young and full adulthood) but a linear significant decline for subjects 9 years or greater (middle age and senescence). In contrast to previous studies that show neurogenesis to decline linearly throughout the lifespan, this study shows that neurogenesis occurs steadily throughout adulthood and begins to decline in middle age in bonnet macaques.
