Background:Chronic hyperuricemia is associated with complications such as gout and uric acid nephropathy,but uric acid also exhibits biological activities(e.g.,antioxidant effects,potential neuroprotective properties ...Background:Chronic hyperuricemia is associated with complications such as gout and uric acid nephropathy,but uric acid also exhibits biological activities(e.g.,antioxidant effects,potential neuroprotective properties against neurodegenerative diseases).Nonhuman primates are ideal models for studying neurodegenerative diseases;however,existing nonhuman primate hyperuricemia models cannot sustain long-term elevated serum uric acid levels,nor recapitulate the impaired uric acid excretion observed in clinical hyperuricemic patients.Methods:First,we detected uricase expression in cynomolgus monkeys and compared it with that in mice.Then,we established a cynomolgus monkey hyperuricemia model by administering a mixture of potassium oxonate,hydrochlorothiazide,and adenine via fruits and vegetables.We further analyzed the regulatory effects of this model on uric acid metabolism(synthesis,degradation,and excretion)and the expression of uric acid transporter genes in the intestine and kidney.Results:Cynomolgus monkeys express functional uricase,but at a lower level than mice.The established model maintained stable,long-term hyperuricemia by three mechanisms:increasing intestinal and renal uric acid excretion load,inhibiting hepatic uric acid degradation,and promoting uric acid synthesis.Additionally,the model downregulated the expression of intestinal/renal uric acid-secreting transporter genes,while upregulating uric acid-reabsorbing transporter genes.Conclusions:This novel cynomolgus monkey hyperuricemia model provides a new tool for investigating the association between hyperuricemia and neurodegenerative diseases,and will help clarify the mechanism by which serum uric acid influences cognitive function.展开更多
Dysphagia is a common complication of stroke,Parkinson's disease(PD),and amyotrophic lateral sclerosis(ALS).The construction of animal models of dysphagia is an important way to explore its pathogenesis and treatm...Dysphagia is a common complication of stroke,Parkinson's disease(PD),and amyotrophic lateral sclerosis(ALS).The construction of animal models of dysphagia is an important way to explore its pathogenesis and treatment.At present,the animal models of dysphagia mainly include rodents,nonhuman primates,and other mammals,such as pigs and dogs.This review systematically summarizes the establishment and evaluation of dysphagia animal models in stroke,PD,and ALS in three kinds of experimental animals,providing a basis for the selection of appropriate animal models of dysphagia.展开更多
Unlike traditional literature where animals are often portrayed allegorically as mere symbols,in Pulitzer Prize winner Jane Smiley’s The Horses of Oak Valley Ranch series,the portrayal of horses underscores their dis...Unlike traditional literature where animals are often portrayed allegorically as mere symbols,in Pulitzer Prize winner Jane Smiley’s The Horses of Oak Valley Ranch series,the portrayal of horses underscores their distinct individuality and autonomy.Focusing on three novels in the series-A Good Horse,True Blue,and Pie in the Sky,this paper analyzes how Smiley crafts a narrative that resists anthropocentrism and validates the subjectivity of nonhuman animals.By examining the unique reactions of horses in various situations,such as their differing facial expressions before a jump,their various responses to feeding and grooming,and their individualistic moving behaviors,this study reveals how Smiley highlights the psychological and physical diversity within a single species.The horses’individual traits are portrayed not as mere animal instinct but as conscious,intentional responses that signify their agency.Drawing on Marc Bekoff’s defense of animal individuality,Val Plumwood’s condemnation of anthropocentrism,and Cynthia Willett’s critique of speciesism,the paper argues that Smiley’s representation of equine individualistic behaviors is an affirmation of the inherent subjectivity of animals.Through these detailed descriptions,Smiley challenges the Cartesian notion of animals as mere automatons and encourages readers to recognize animals as complex individuals.Ultimately,this study emphasizes the significance of acknowledging animal subjectivity in fostering a more ethical and harmonious human-animal relationship.展开更多
Anesthesia plays a crucial role in regulating physiological states during medical procedures,but its effects on neural activity remain incompletely understood,particularly at the prefrontal cortical level.The prefront...Anesthesia plays a crucial role in regulating physiological states during medical procedures,but its effects on neural activity remain incompletely understood,particularly at the prefrontal cortical level.The prefrontal cortex is essential for various cognitive and motor functions,yet high-spatiotemporal-resolution electrodes at the cellular level remain challenging to develop,which has hindered the acquisition of detailed electrophysiological data from anesthetized subjects.Here,we design a 16-channel silicon-based microelectrode array(MEA),which,after modification with platinum black nanoparticles,exhibits significantly reduced impedance(22.5 kΩ)and increased phase(−33.5°),enhancing its electrical performance and electrophysiological signal detection capabilities.Using this modified MEA,we have recorded cellular-level neural activity during the recovery process of a rhesus macaque following prolonged anesthesia.Over a 660 s period,we observed a gradual increase in the neuronal firing rate in the F7 area,along with distinctive patterns in local field potentials across different frequency bands.Notably,power in the δ and θ bands increased continuously during recovery,highlighting their potential role in the transition from anesthesia to wakefulness.Our findings provide new insights into the dynamic recovery process of cortical neurons and offer a powerful tool for high-spatiotemporal-resolution neural monitoring in nonhuman primates.展开更多
Alcohol abuse is a global problem due to the financial burden on society and the healthcare system. While the harmful health effects of chronic alcohol abuse are well established, more recent data suggest that acute a...Alcohol abuse is a global problem due to the financial burden on society and the healthcare system. While the harmful health effects of chronic alcohol abuse are well established, more recent data suggest that acute alcohol consumption also affects human wellbeing. Thus, there is a need for research models in order to fully understand the effect of acute alcohol abuse on different body systems and organs. The present manuscript summarizes the interdisciplinary advantages and disadvantages of currently available human and non-human models of acute alcohol abuse, and identifi es their suitability for biomedical research.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
Social stability in group-living animals is an emergent property which arises from the interaction amongst multiple behavioral networks. However, pinpointing when a social group is at risk of collapse is difficult. We...Social stability in group-living animals is an emergent property which arises from the interaction amongst multiple behavioral networks. However, pinpointing when a social group is at risk of collapse is difficult. We used a joint network model- ing approach to examine the interdependencies between two behavioral networks, aggression and status signaling, from four sta- ble and three unstable groups of rhesus macaques in order to identify characteristic patterns of network interdependence in stable groups that are readily distinguishable from unstable groups. Our results showed that the most prominent source of aggres- sion-status network interdependence in stable social groups came from more frequent dyads than expected with opposite direc- tion status-aggression （i.e. A threatens B and B signals acceptance of subordinate status）. In contrast, unstable groups showed a decrease in opposite direction aggression-status dyads （but remained higher than expected） as well as more frequent than ex- pected dyads with bidirectional aggression. These results demonstrate that not only was the stable joint relationship between ag- gression and status networks readily distinguishable from unstable time points, social instability manifested in at least two differ- ent ways. In sum, our joint modeling approach may prove useful in quantifying and monitoring the complex social dynamics of any wild or captive social system, as all social systems are composed of multiple interconnected networks [Current Zoology 61 （1）： 70-84, 2015].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
Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested c...Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.展开更多
Virtual simulated environments provide multiple ways of testing cognitive function and evaluatingproblem solving with humans （e.g., Woollett et al. 2009）. The use of such interactive technologyhas increasingly becom...Virtual simulated environments provide multiple ways of testing cognitive function and evaluatingproblem solving with humans （e.g., Woollett et al. 2009）. The use of such interactive technologyhas increasingly become an essential part of modern life （e.g., autonomously driving vehicles, glo-bal positioning systems （GPS）, and touchscreen computers; Chinn and Fairlie 2007; Brown 2011）.While many nonhuman animals have their own forms of technology, such as chimpanzees whocreate and use tools, in captive animal environments the opportunity to actively participate withinteractive technology is not often made available. Exceptions can be found in some state-of-the-art zoos and laboratory facilities （e.g., Mallavarapu and Kuhar 2005）. When interactive technologyis available, captive animals often selectively choose to engage with it. This enhances the animal＇ssense of control over their immediate surroundings （e.g., Clay et al. 2011; Ackerman 2012）. Suchself-efficacy may help to fulfill basic requirements in a species＇ daily activities using problem solv-ing that can involve foraging and other goal-oriented behaviors. It also assists in fulfilling thestrong underlying motivation for contrafreeloading and exploration expressed behaviorally bymany species in captivity （Young 1999）. Moreover, being able to present nonhuman primates vir-tual reality environments under experimental conditions provides the opportunity to gain insightinto their navigational abilities and spatial cognition. It allows for insight into the generation andapplication of internal mental representations of landmarks and environments under multiple con-ditions （e.g., small- and large-scale space） and subsequent spatial behavior. This paper reviewsmethods using virtual reality developed to investigate the spatial cognitive abilities of nonhumanprimates, and great apes in particular, in comparison with that of humans of multiple age groups.We make recommendations about training, best practices, and also pitfalls to avoid.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
Nonhuman culture was first considered in nonhuman primates because they are genetically similar to humans. How- ever, evolution is not progressive and therefore many species may occupy niches that favor socially trans...Nonhuman culture was first considered in nonhuman primates because they are genetically similar to humans. How- ever, evolution is not progressive and therefore many species may occupy niches that favor socially transmitted, group specific behavior. Not surprisingly, evidence for culture has accrued in several taxonomic groups, including cetaceans. If culture is an ada- ptation, it is imperative we understand the factors that favor its formation. Understanding the evolutionary origin of culture will allow for a wider range of species to be studied, including those that are difficult to test in the laboratory. I propose a broad-based functional paradigm for evaluating nonhuman culture; based on the idea that while not all cultural behaviors may garner fitness benefits to the individual, the ecological and social environments in which cultural behaviors evolved must have favored the physical attributes and social learning capabilities that allow for cultural formation. Specifically this framework emphasizes the relationships between social learning, ecology, social systems, and biology in relation to culture. I illustrate the utility of the func- tional paradigm with evidence from the ceteacean group, while setting the stage for a stringent species by species analysis. By means of contextualizing culture, the Functional Paradigm can evaluate a species＇ potential to exhibit culture and can investigate potentially cultural behaviors展开更多
Understanding gene expression variations between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques(Macaca mulatta, MMU)and crab-eating macaques(M. fascicularis, MFA) serve as...Understanding gene expression variations between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques(Macaca mulatta, MMU)and crab-eating macaques(M. fascicularis, MFA) serve as crucial nonhuman primate biomedical models with different phenotypes. To date, however, large-scale comparative transcriptome research between these two species has not yet been fully explored. Here, we conducted systematic comparisons utilizing newly sequenced RNA-seq data from84 samples(41 MFA samples and 43 MMU samples)encompassing 14 common tissues. Our findings revealed a small fraction of genes(3.7%) with differential expression between the two species, as well as 36.5% of genes with tissue-specific expression in both macaques. Comparison of gene expression between macaques and humans indicated that 22.6% of orthologous genes displayed differential expression in at least two tissues. Moreover,19.41% of genes that overlapped with macaque-specific structural variants showed differential expression between humans and macaques. Of these, the FAM220A gene exhibited elevated expression in humans compared to macaques due to lineage-specific duplication. In summary,this study presents a large-scale transcriptomic comparison between MMU and MFA and between macaques and humans. The discovery of gene expression variations not only enhances the biomedical utility of macaque models but also contributes to the wider field of primate genomics.展开更多
The hepatitis B virus(HBV)is a cosmopolitan infectious agent currently affecting over 350 million people worldwide,presently accounting for more than two billion infections.In addition to man,other hepatitis virus str...The hepatitis B virus(HBV)is a cosmopolitan infectious agent currently affecting over 350 million people worldwide,presently accounting for more than two billion infections.In addition to man,other hepatitis virus strains infect species of several mammalian families of the Primates,Rodentia and Chiroptera orders,in addition to birds.The mounting evidence of HBV infection in African,Asian and neotropical primates draws attention to the potential crossspecies,zoonotic transmission of these viruses to man.Moreover,recent evidence also suggests the humans may also function as a source of viral infection to other mammals,particularly to domestic animals like poultry and swine.In this review,we list all evidence of HBV and HBVlike infection of nonhuman mammals and discuss their potential roles as donors or recipients of these viruses to humans and to other closely-related species.展开更多
BACKGROUND The development of regenerative therapy for human spinal cord injury(SCI)is dramatically restricted by two main challenges:the need for a safe source of functionally active and reproducible neural stem cell...BACKGROUND The development of regenerative therapy for human spinal cord injury(SCI)is dramatically restricted by two main challenges:the need for a safe source of functionally active and reproducible neural stem cells and the need of adequate animal models for preclinical testing.Direct reprogramming of somatic cells into neuronal and glial precursors might be a promising solution to the first challenge.The use of non-human primates for preclinical studies exploring new treatment paradigms in SCI results in data with more translational relevance to human SCI.AIM To investigate the safety and efficacy of intraspinal transplantation of directly reprogrammed neural precursor cells(drNPCs).METHODS Seven non-human primates with verified complete thoracic SCI were divided into two groups:drNPC group(n=4)was subjected to intraspinal transplantation of 5 million drNPCs rostral and caudal to the lesion site 2 wk post injury,and lesion control(n=3)was injected identically with the equivalent volume of vehicle.RESULTS Follow-up for 12 wk revealed that animals in the drNPC group demonstrated a significant recovery of the paralyzed hindlimb as well as recovery of somatosensory evoked potential and motor evoked potential of injured pathways.Magnetic resonance diffusion tensor imaging data confirmed the intraspinal transplantation of drNPCs did not adversely affect the morphology of the central nervous system or cerebrospinal fluid circulation.Subsequent immunohistochemical analysis showed that drNPCs maintained SOX2 expression characteristic of multipotency in the transplanted spinal cord for at least 12 wk,migrating to areas of axon growth cones.CONCLUSION Our data demonstrated that drNPC transplantation was safe and contributed to improvement of spinal cord function after acute SCI,based on neurological status assessment and neurophysiological recovery within 12 wk after transplantation.The functional improvement described was not associated with neuronal differentiation of the allogeneic drNPCs.Instead,directed drNPCs migration to the areas of active growth cone formation may provide exosome and paracrine trophic support,thereby further supporting the regeneration processes.展开更多
No study has reported the safety, effectiveness, and consistency of endovascular middle cerebral artery occlusion in a chronic cerebral ischemia model. Nor have studies verified the safest and most effective segment, ...No study has reported the safety, effectiveness, and consistency of endovascular middle cerebral artery occlusion in a chronic cerebral ischemia model. Nor have studies verified the safest and most effective segment, or branch, in the embolic middle cerebral artery. In this experiment, cerebral infarction models were established at M1, and on the upper and lower trunks on the contralateral side of the handedness of rhesus monkeys by using endovascular intervention. The results confirmed a high animal survival rate in stroke models of middle cerebral artery upper trunk occlusion. There was pronounced paralysis at the acute phase, long-term upper extremity dysfunction at the chronic phase, and the models showed good repeatability and consistency. Thus, this study describes a safe and effective model of chronic stroke.展开更多
The feasibility of a commercially available assay for C-reactive protein(CRP,CRP for humans:hCRP,and CRP for dogs:vCRP)and a trial reagent of serum amyloid A(SAA,vSAA for animals)were applied to the measurement of acu...The feasibility of a commercially available assay for C-reactive protein(CRP,CRP for humans:hCRP,and CRP for dogs:vCRP)and a trial reagent of serum amyloid A(SAA,vSAA for animals)were applied to the measurement of acute phase proteins in zoo animals,particularly in nonhuman primates and feline carnivores was evaluate.Results showed that hCRP and vSAA methods were applicable to measure CRP and SAA in Haplorhini.There was a highly signifcant correlation between both parameters with remarkably high correlation coefcient.A higher proportion of Bonnet macaques in Haplorhini,and the linear regression with good correlation between hCRP and vSAA levels were observed.Reference values in healthy Bonnet macaques were hCRP(46.86±30.97 nmol/L)and vSAA(9.06±1.95μg/mL).Although Ring-tailed lemur,which belonging to Strepsirrhini,showed low vSAA concentrations(reference values:1.08±0.47μg/mL),vSAA in patients was apparently elevated.The vCRP and vSAA methods were applicable to measurements of CRP and SAA in feline carnivores for highly signifcant correlation between both parameters.Theses two methods were also been deteded in lions,tigers and cheetahs.vSAA assays can be applied to measure SAA levels in other carnivores and herbivores.In conclusion,vSAA systems have potential utility as diagnostic tools for health screening and prediction in zoo animals.展开更多
Background:Chronic kidney disease(CKD)has a high global prevalence and large unmet need.Central to developing new CKD therapies are in vivo models in CKD.However,next-generation antibody,protein,and gene therapies are...Background:Chronic kidney disease(CKD)has a high global prevalence and large unmet need.Central to developing new CKD therapies are in vivo models in CKD.However,next-generation antibody,protein,and gene therapies are highly specific,meaning some do not cross-react with rodent targets.This complicates preclinical development,as established in vivo rodent models cannot be utilized unless tool therapeutics are also developed.Tool compounds can be difficult to develop and,if available,typically have different epitopes,sequences,and/or altered affinity,making it unclear how efficacious the lead therapeutic may be,or what dosing regimen to investigate.To address this,we aimed to develop a nonhuman primate model of CKD.Methods:In vivo rodent unilateral ureteral obstruction(UUO)models kidney fibrosis and is commonly used due to its rapidity,consistency,and ease.We describe translation of this model to the cynomolgus monkey,specifically optimizing the model duration to allow adequate time for assessment of novel therapeutics prior to the fibrotic plateau.Results:We demonstrated that disease developed more slowly in cynomolgus monkeys than in rodents post-UUO,with advanced fibrosis developing by 6 weeks.The tubulointerstitial fibrosis in cynomolgus monkeys was more consistent with human obstructive disease than in rodents,having a more aggressive tubular basement expansion and a higher fibroblast infiltration.The fibrosis was also associated with increased transglutaminase activity,consistent with that seen in patients with CKD.Conclusion:This cynomolgus monkey UUO model can be used to test potential human-specific therapeutics in kidney fibrosis.展开更多
Backgrounds:Streptozotocin(STZ)-induced diabetic monkey is a wide used preclinical animal model for the investigation of diabetes such as islet transplantation and development of diabetic drugs.There are serious side ...Backgrounds:Streptozotocin(STZ)-induced diabetic monkey is a wide used preclinical animal model for the investigation of diabetes such as islet transplantation and development of diabetic drugs.There are serious side effects of this method,including nausea,emesis,weight loss,liver damage,renal failure,and metabolic acidosis.In order to reduce the side effects,diabetic monkeys were induced using clinicalgrade STZ.However,clinical-grade STZ is not available in China.Here,we establised a method by using 100 mg/kg analytical-grade STZ to induce complete diabetes in cynomolgus monkey without generating adverse effects to liver and renal.Methods:Three cynomolgus monkeys were used in this study.100 mg/kg STZ dissolved in normal saline and infused through vein line in 5 minutes after indwelling catheter in the carotid artery and jugular vein.After the STZ administration,blood glucose levels were examined every 1 or 2 hours in the first 48 hours.Then,blood glucose levels were examined twice per day during the first week after the STZ injection.Insulin and C-peptide levels were measured by ELISA.Blood chemistry of hepatic and renal function tests were performed.Insulin and glucagon expression in the islet of diabetic monkey and normal monkey were examined by immunohistochemistry assays.Results:The stimulated C-peptide level(Intravenous glucose tolerance test)which is less than 0.5 ng/mL,the triphasic blood glucose response and the destroyed β cell suggested the complete induction of diabetes model.No apparent adverse effects were observed including no signs of vomiting and toxicity after STZ injection.Conclusion:In summary,we established a safe and reproducible STZ-induced diabetic cynomolgus monkey model for islet transplantation which will be used to develop novel approaches for the treatment of diabetes.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The Yunnan“Xingdian Talent Program”Yunling Scholar Project,(Grant No.CA24129L025A)National Natural Science Foundation of China,Grant/Award Number:32160157 and 82160564Major Science and Technology Project of Yunnan Province(Grant No.202202AG050008)。
文摘Background:Chronic hyperuricemia is associated with complications such as gout and uric acid nephropathy,but uric acid also exhibits biological activities(e.g.,antioxidant effects,potential neuroprotective properties against neurodegenerative diseases).Nonhuman primates are ideal models for studying neurodegenerative diseases;however,existing nonhuman primate hyperuricemia models cannot sustain long-term elevated serum uric acid levels,nor recapitulate the impaired uric acid excretion observed in clinical hyperuricemic patients.Methods:First,we detected uricase expression in cynomolgus monkeys and compared it with that in mice.Then,we established a cynomolgus monkey hyperuricemia model by administering a mixture of potassium oxonate,hydrochlorothiazide,and adenine via fruits and vegetables.We further analyzed the regulatory effects of this model on uric acid metabolism(synthesis,degradation,and excretion)and the expression of uric acid transporter genes in the intestine and kidney.Results:Cynomolgus monkeys express functional uricase,but at a lower level than mice.The established model maintained stable,long-term hyperuricemia by three mechanisms:increasing intestinal and renal uric acid excretion load,inhibiting hepatic uric acid degradation,and promoting uric acid synthesis.Additionally,the model downregulated the expression of intestinal/renal uric acid-secreting transporter genes,while upregulating uric acid-reabsorbing transporter genes.Conclusions:This novel cynomolgus monkey hyperuricemia model provides a new tool for investigating the association between hyperuricemia and neurodegenerative diseases,and will help clarify the mechanism by which serum uric acid influences cognitive function.
基金National Natural Science Foundation of China,Grant/Award Number:82172531Joint Funds for the Innovation of Science and Technology,Fujian Province,Grant/Award Number:2021Y9105。
文摘Dysphagia is a common complication of stroke,Parkinson's disease(PD),and amyotrophic lateral sclerosis(ALS).The construction of animal models of dysphagia is an important way to explore its pathogenesis and treatment.At present,the animal models of dysphagia mainly include rodents,nonhuman primates,and other mammals,such as pigs and dogs.This review systematically summarizes the establishment and evaluation of dysphagia animal models in stroke,PD,and ALS in three kinds of experimental animals,providing a basis for the selection of appropriate animal models of dysphagia.
文摘Unlike traditional literature where animals are often portrayed allegorically as mere symbols,in Pulitzer Prize winner Jane Smiley’s The Horses of Oak Valley Ranch series,the portrayal of horses underscores their distinct individuality and autonomy.Focusing on three novels in the series-A Good Horse,True Blue,and Pie in the Sky,this paper analyzes how Smiley crafts a narrative that resists anthropocentrism and validates the subjectivity of nonhuman animals.By examining the unique reactions of horses in various situations,such as their differing facial expressions before a jump,their various responses to feeding and grooming,and their individualistic moving behaviors,this study reveals how Smiley highlights the psychological and physical diversity within a single species.The horses’individual traits are portrayed not as mere animal instinct but as conscious,intentional responses that signify their agency.Drawing on Marc Bekoff’s defense of animal individuality,Val Plumwood’s condemnation of anthropocentrism,and Cynthia Willett’s critique of speciesism,the paper argues that Smiley’s representation of equine individualistic behaviors is an affirmation of the inherent subjectivity of animals.Through these detailed descriptions,Smiley challenges the Cartesian notion of animals as mere automatons and encourages readers to recognize animals as complex individuals.Ultimately,this study emphasizes the significance of acknowledging animal subjectivity in fostering a more ethical and harmonious human-animal relationship.
基金sponsored by the National Key R&D Program of China(Grant Nos.2022YFC2402500 and 2022YFB3205602)the National Natural Science Foundation of China(Grant Nos.62121003,T2293730,T2293731,62333020,62171434,62471291)+2 种基金the Major Program of Scientific and Technical Innovation 2030(Grant No.2021ZD02016030)the Joint Foundation Program of the Chinese Academy of Sciences(Grant No.8091A170201)the Scientific Instrument Developing Project of the Chinese Academy of Sciences(Grant No.PTYQ2024BJ0009).
文摘Anesthesia plays a crucial role in regulating physiological states during medical procedures,but its effects on neural activity remain incompletely understood,particularly at the prefrontal cortical level.The prefrontal cortex is essential for various cognitive and motor functions,yet high-spatiotemporal-resolution electrodes at the cellular level remain challenging to develop,which has hindered the acquisition of detailed electrophysiological data from anesthetized subjects.Here,we design a 16-channel silicon-based microelectrode array(MEA),which,after modification with platinum black nanoparticles,exhibits significantly reduced impedance(22.5 kΩ)and increased phase(−33.5°),enhancing its electrical performance and electrophysiological signal detection capabilities.Using this modified MEA,we have recorded cellular-level neural activity during the recovery process of a rhesus macaque following prolonged anesthesia.Over a 660 s period,we observed a gradual increase in the neuronal firing rate in the F7 area,along with distinctive patterns in local field potentials across different frequency bands.Notably,power in the δ and θ bands increased continuously during recovery,highlighting their potential role in the transition from anesthesia to wakefulness.Our findings provide new insights into the dynamic recovery process of cortical neurons and offer a powerful tool for high-spatiotemporal-resolution neural monitoring in nonhuman primates.
基金Supported by Grants AA016571 (AD)AA014372 (GS) from NIAAAA (in part)
文摘Alcohol abuse is a global problem due to the financial burden on society and the healthcare system. While the harmful health effects of chronic alcohol abuse are well established, more recent data suggest that acute alcohol consumption also affects human wellbeing. Thus, there is a need for research models in order to fully understand the effect of acute alcohol abuse on different body systems and organs. The present manuscript summarizes the interdisciplinary advantages and disadvantages of currently available human and non-human models of acute alcohol abuse, and identifi es their suitability for biomedical research.
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.
文摘Social stability in group-living animals is an emergent property which arises from the interaction amongst multiple behavioral networks. However, pinpointing when a social group is at risk of collapse is difficult. We used a joint network model- ing approach to examine the interdependencies between two behavioral networks, aggression and status signaling, from four sta- ble and three unstable groups of rhesus macaques in order to identify characteristic patterns of network interdependence in stable groups that are readily distinguishable from unstable groups. Our results showed that the most prominent source of aggres- sion-status network interdependence in stable social groups came from more frequent dyads than expected with opposite direc- tion status-aggression （i.e. A threatens B and B signals acceptance of subordinate status）. In contrast, unstable groups showed a decrease in opposite direction aggression-status dyads （but remained higher than expected） as well as more frequent than ex- pected dyads with bidirectional aggression. These results demonstrate that not only was the stable joint relationship between ag- gression and status networks readily distinguishable from unstable time points, social instability manifested in at least two differ- ent ways. In sum, our joint modeling approach may prove useful in quantifying and monitoring the complex social dynamics of any wild or captive social system, as all social systems are composed of multiple interconnected networks [Current Zoology 61 （1）： 70-84, 2015].
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 National Natural Science Foundation of China,No.81000852 and 81301677the AHA Award,No.17POST32530004+1 种基金the Supporting Project of Science & Technology of Sichuan Province of China,No.2012SZ0140the Research Foundation of Zhejiang Province of China,No.201022896
文摘Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.
文摘Virtual simulated environments provide multiple ways of testing cognitive function and evaluatingproblem solving with humans （e.g., Woollett et al. 2009）. The use of such interactive technologyhas increasingly become an essential part of modern life （e.g., autonomously driving vehicles, glo-bal positioning systems （GPS）, and touchscreen computers; Chinn and Fairlie 2007; Brown 2011）.While many nonhuman animals have their own forms of technology, such as chimpanzees whocreate and use tools, in captive animal environments the opportunity to actively participate withinteractive technology is not often made available. Exceptions can be found in some state-of-the-art zoos and laboratory facilities （e.g., Mallavarapu and Kuhar 2005）. When interactive technologyis available, captive animals often selectively choose to engage with it. This enhances the animal＇ssense of control over their immediate surroundings （e.g., Clay et al. 2011; Ackerman 2012）. Suchself-efficacy may help to fulfill basic requirements in a species＇ daily activities using problem solv-ing that can involve foraging and other goal-oriented behaviors. It also assists in fulfilling thestrong underlying motivation for contrafreeloading and exploration expressed behaviorally bymany species in captivity （Young 1999）. Moreover, being able to present nonhuman primates vir-tual reality environments under experimental conditions provides the opportunity to gain insightinto their navigational abilities and spatial cognition. It allows for insight into the generation andapplication of internal mental representations of landmarks and environments under multiple con-ditions （e.g., small- and large-scale space） and subsequent spatial behavior. This paper reviewsmethods using virtual reality developed to investigate the spatial cognitive abilities of nonhumanprimates, and great apes in particular, in comparison with that of humans of multiple age groups.We make recommendations about training, best practices, and also pitfalls to avoid.
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Nonhuman culture was first considered in nonhuman primates because they are genetically similar to humans. How- ever, evolution is not progressive and therefore many species may occupy niches that favor socially transmitted, group specific behavior. Not surprisingly, evidence for culture has accrued in several taxonomic groups, including cetaceans. If culture is an ada- ptation, it is imperative we understand the factors that favor its formation. Understanding the evolutionary origin of culture will allow for a wider range of species to be studied, including those that are difficult to test in the laboratory. I propose a broad-based functional paradigm for evaluating nonhuman culture; based on the idea that while not all cultural behaviors may garner fitness benefits to the individual, the ecological and social environments in which cultural behaviors evolved must have favored the physical attributes and social learning capabilities that allow for cultural formation. Specifically this framework emphasizes the relationships between social learning, ecology, social systems, and biology in relation to culture. I illustrate the utility of the func- tional paradigm with evidence from the ceteacean group, while setting the stage for a stringent species by species analysis. By means of contextualizing culture, the Functional Paradigm can evaluate a species＇ potential to exhibit culture and can investigate potentially cultural behaviors
基金supported by the National Natural Science Foundation of China (82021001 and 31825018 to Q.S., 32370658 to Y.M.,82001372 to X.Y.)National Key Research and Development Program of China (2022YFF0710901)+2 种基金National Science and Technology Innovation2030 Major Program (2021ZD0200900) to Q.S.Shanghai Pujiang Program (22PJ1407300)Shanghai Jiao Tong University 2030 Initiative (WH510363001-7) to Y.M。
文摘Understanding gene expression variations between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques(Macaca mulatta, MMU)and crab-eating macaques(M. fascicularis, MFA) serve as crucial nonhuman primate biomedical models with different phenotypes. To date, however, large-scale comparative transcriptome research between these two species has not yet been fully explored. Here, we conducted systematic comparisons utilizing newly sequenced RNA-seq data from84 samples(41 MFA samples and 43 MMU samples)encompassing 14 common tissues. Our findings revealed a small fraction of genes(3.7%) with differential expression between the two species, as well as 36.5% of genes with tissue-specific expression in both macaques. Comparison of gene expression between macaques and humans indicated that 22.6% of orthologous genes displayed differential expression in at least two tissues. Moreover,19.41% of genes that overlapped with macaque-specific structural variants showed differential expression between humans and macaques. Of these, the FAM220A gene exhibited elevated expression in humans compared to macaques due to lineage-specific duplication. In summary,this study presents a large-scale transcriptomic comparison between MMU and MFA and between macaques and humans. The discovery of gene expression variations not only enhances the biomedical utility of macaque models but also contributes to the wider field of primate genomics.
基金Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico of Brazil,No.303422/2010-6
文摘The hepatitis B virus(HBV)is a cosmopolitan infectious agent currently affecting over 350 million people worldwide,presently accounting for more than two billion infections.In addition to man,other hepatitis virus strains infect species of several mammalian families of the Primates,Rodentia and Chiroptera orders,in addition to birds.The mounting evidence of HBV infection in African,Asian and neotropical primates draws attention to the potential crossspecies,zoonotic transmission of these viruses to man.Moreover,recent evidence also suggests the humans may also function as a source of viral infection to other mammals,particularly to domestic animals like poultry and swine.In this review,we list all evidence of HBV and HBVlike infection of nonhuman mammals and discuss their potential roles as donors or recipients of these viruses to humans and to other closely-related species.
基金Supported by Russian Science Foundation,No.16-15-10432。
文摘BACKGROUND The development of regenerative therapy for human spinal cord injury(SCI)is dramatically restricted by two main challenges:the need for a safe source of functionally active and reproducible neural stem cells and the need of adequate animal models for preclinical testing.Direct reprogramming of somatic cells into neuronal and glial precursors might be a promising solution to the first challenge.The use of non-human primates for preclinical studies exploring new treatment paradigms in SCI results in data with more translational relevance to human SCI.AIM To investigate the safety and efficacy of intraspinal transplantation of directly reprogrammed neural precursor cells(drNPCs).METHODS Seven non-human primates with verified complete thoracic SCI were divided into two groups:drNPC group(n=4)was subjected to intraspinal transplantation of 5 million drNPCs rostral and caudal to the lesion site 2 wk post injury,and lesion control(n=3)was injected identically with the equivalent volume of vehicle.RESULTS Follow-up for 12 wk revealed that animals in the drNPC group demonstrated a significant recovery of the paralyzed hindlimb as well as recovery of somatosensory evoked potential and motor evoked potential of injured pathways.Magnetic resonance diffusion tensor imaging data confirmed the intraspinal transplantation of drNPCs did not adversely affect the morphology of the central nervous system or cerebrospinal fluid circulation.Subsequent immunohistochemical analysis showed that drNPCs maintained SOX2 expression characteristic of multipotency in the transplanted spinal cord for at least 12 wk,migrating to areas of axon growth cones.CONCLUSION Our data demonstrated that drNPC transplantation was safe and contributed to improvement of spinal cord function after acute SCI,based on neurological status assessment and neurophysiological recovery within 12 wk after transplantation.The functional improvement described was not associated with neuronal differentiation of the allogeneic drNPCs.Instead,directed drNPCs migration to the areas of active growth cone formation may provide exosome and paracrine trophic support,thereby further supporting the regeneration processes.
基金the National Key Technology Research and Development Program during Eleventh Five-Year Plan, No. 2006BAI01A14
文摘No study has reported the safety, effectiveness, and consistency of endovascular middle cerebral artery occlusion in a chronic cerebral ischemia model. Nor have studies verified the safest and most effective segment, or branch, in the embolic middle cerebral artery. In this experiment, cerebral infarction models were established at M1, and on the upper and lower trunks on the contralateral side of the handedness of rhesus monkeys by using endovascular intervention. The results confirmed a high animal survival rate in stroke models of middle cerebral artery upper trunk occlusion. There was pronounced paralysis at the acute phase, long-term upper extremity dysfunction at the chronic phase, and the models showed good repeatability and consistency. Thus, this study describes a safe and effective model of chronic stroke.
文摘The feasibility of a commercially available assay for C-reactive protein(CRP,CRP for humans:hCRP,and CRP for dogs:vCRP)and a trial reagent of serum amyloid A(SAA,vSAA for animals)were applied to the measurement of acute phase proteins in zoo animals,particularly in nonhuman primates and feline carnivores was evaluate.Results showed that hCRP and vSAA methods were applicable to measure CRP and SAA in Haplorhini.There was a highly signifcant correlation between both parameters with remarkably high correlation coefcient.A higher proportion of Bonnet macaques in Haplorhini,and the linear regression with good correlation between hCRP and vSAA levels were observed.Reference values in healthy Bonnet macaques were hCRP(46.86±30.97 nmol/L)and vSAA(9.06±1.95μg/mL).Although Ring-tailed lemur,which belonging to Strepsirrhini,showed low vSAA concentrations(reference values:1.08±0.47μg/mL),vSAA in patients was apparently elevated.The vCRP and vSAA methods were applicable to measurements of CRP and SAA in feline carnivores for highly signifcant correlation between both parameters.Theses two methods were also been deteded in lions,tigers and cheetahs.vSAA assays can be applied to measure SAA levels in other carnivores and herbivores.In conclusion,vSAA systems have potential utility as diagnostic tools for health screening and prediction in zoo animals.
基金This study was funded by UCB PharmaAnimal work was approved by Prisys Institutional Animal Care and Use Committee under study number 2015-PS11-002(license code SYXK-2014-007).
文摘Background:Chronic kidney disease(CKD)has a high global prevalence and large unmet need.Central to developing new CKD therapies are in vivo models in CKD.However,next-generation antibody,protein,and gene therapies are highly specific,meaning some do not cross-react with rodent targets.This complicates preclinical development,as established in vivo rodent models cannot be utilized unless tool therapeutics are also developed.Tool compounds can be difficult to develop and,if available,typically have different epitopes,sequences,and/or altered affinity,making it unclear how efficacious the lead therapeutic may be,or what dosing regimen to investigate.To address this,we aimed to develop a nonhuman primate model of CKD.Methods:In vivo rodent unilateral ureteral obstruction(UUO)models kidney fibrosis and is commonly used due to its rapidity,consistency,and ease.We describe translation of this model to the cynomolgus monkey,specifically optimizing the model duration to allow adequate time for assessment of novel therapeutics prior to the fibrotic plateau.Results:We demonstrated that disease developed more slowly in cynomolgus monkeys than in rodents post-UUO,with advanced fibrosis developing by 6 weeks.The tubulointerstitial fibrosis in cynomolgus monkeys was more consistent with human obstructive disease than in rodents,having a more aggressive tubular basement expansion and a higher fibroblast infiltration.The fibrosis was also associated with increased transglutaminase activity,consistent with that seen in patients with CKD.Conclusion:This cynomolgus monkey UUO model can be used to test potential human-specific therapeutics in kidney fibrosis.
基金This work were supported by grants from the National Key R&D Program of China(2017YFC1103704)Special Funds for the Construction of High Level Hospitals in Guangdong Province(2019),Sanming Project of Medicine in Shenzhen(SZSM201412020)+6 种基金Fund for High Level Medical Discipline Construction of Shenzhen(2016031638)National Science Foundation for Distinguished Yong Scholars of Guangdong province(2016A030306051)National Science Foundation(81701383)National Science Foundation for Postdoctoral Startup of Guangdong province(2017A030310005)China Postdoctoral Science Foundation(2015M580755)China Postdoctoral Science Special Foundation(2016T90813)Shenzhen Foundation of Health and Family Planning Commission(SZXJ2017021).
文摘Backgrounds:Streptozotocin(STZ)-induced diabetic monkey is a wide used preclinical animal model for the investigation of diabetes such as islet transplantation and development of diabetic drugs.There are serious side effects of this method,including nausea,emesis,weight loss,liver damage,renal failure,and metabolic acidosis.In order to reduce the side effects,diabetic monkeys were induced using clinicalgrade STZ.However,clinical-grade STZ is not available in China.Here,we establised a method by using 100 mg/kg analytical-grade STZ to induce complete diabetes in cynomolgus monkey without generating adverse effects to liver and renal.Methods:Three cynomolgus monkeys were used in this study.100 mg/kg STZ dissolved in normal saline and infused through vein line in 5 minutes after indwelling catheter in the carotid artery and jugular vein.After the STZ administration,blood glucose levels were examined every 1 or 2 hours in the first 48 hours.Then,blood glucose levels were examined twice per day during the first week after the STZ injection.Insulin and C-peptide levels were measured by ELISA.Blood chemistry of hepatic and renal function tests were performed.Insulin and glucagon expression in the islet of diabetic monkey and normal monkey were examined by immunohistochemistry assays.Results:The stimulated C-peptide level(Intravenous glucose tolerance test)which is less than 0.5 ng/mL,the triphasic blood glucose response and the destroyed β cell suggested the complete induction of diabetes model.No apparent adverse effects were observed including no signs of vomiting and toxicity after STZ injection.Conclusion:In summary,we established a safe and reproducible STZ-induced diabetic cynomolgus monkey model for islet transplantation which will be used to develop novel approaches for the treatment of diabetes.
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.
