1.Modeling Parkinson's disease in the common marmoset (Callithrix jacchus): overview of models, methods, and animal care.
Jun Won YUN ; Jae Bum AHN ; Byeong Cheol KANG
Laboratory Animal Research 2015;31(4):155-165
The common marmoset (Callithrix jacchus) is a small-bodied, popular New World monkey and is used widely in reproductive biology, neuroscience, and drug development, due to its comparative ease of handling, high reproductive efficiency, and its unique behavioral characters. In this review, we discuss the marmoset models in Parkinson's disease (PD), which is a neurological movement disorder primarily resulting from a degeneration of dopaminergic neurons with clinical features of tremor, rigidity, postural instability, and akinesia. The most common PD models involve the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine to study the pathogenesis and to evaluate novel therapies. Following the systemic or local administration of these neurotoxins, the marmosets with very severe Parkinson's symptoms are recommended to be placed in an intensive care unit with artificial feeding to increase survival rate. All procedures with MPTP should be conducted in a special room with enclosed cages under negative-pressure by trained researchers with personal protection. Behavioral tests are conducted to provide an external measure of the brain pathology. Along with several biomarkers, including alpha-synuclein and DJ-1, non-invasive neuroimaging techniques such as positron emission tomography and magnetic resonance imaging are used to evaluate the functional changes associated with PD. With the recent growing interest in potential and novel therapies such as stem cell and gene therapy for PD in Korea, the marmoset can be considered as a suitable non-human primate model in PD research to bridge the gap between rodent studies and clinical applications.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
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alpha-Synuclein
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Animals*
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Biomarkers
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Biology
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Brain Diseases
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Callithrix*
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Dopaminergic Neurons
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Genetic Therapy
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Humans
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Intensive Care Units
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Korea
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Magnetic Resonance Imaging
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Methods*
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Models, Animal
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Movement Disorders
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Neuroimaging
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Neurosciences
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Neurotoxins
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Nutritional Support
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Oxidopamine
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Parkinson Disease*
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Platyrrhini
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Positron-Emission Tomography
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Primates
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Rodentia
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Stem Cells
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Survival Rate
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Tremor
2.Genomic Features of Retroelements and Implications for Human Disease.
Genomics & Informatics 2005;3(4):133-141
Most of the endogenous retroviral genes integrated into the primate genome after the split of New World monkeys in the Oligocene era, approximately 33 million years ago. Because they can change the structure of adjacent genes and move between and within chromosomes they may play important roles in evolutionas well as in many kinds of disease and the creation of genetic polymorphism. Comparative analysis of HERVs (human endogenous retroviruses) and their LTR (long terminal repeat) elements in the primate genomes will help us to understand the possible impact of HERV elements in the evolution and phylogeny of primates. For example, HERV-K LTR and SINE-R elements have been identified that have been subject to recent change in the course of primate evolution. They are specific elements to the human genome and could be related to biological function. The HERV-M element is related to the superfamily of HERV-K and is integrated into the periphilin gene as the truncated form, 5'LTR-gag-pol-3'LTR. PCR and RT-PCR approaches indicated that the insertion of various retrotransposable elements in a common ancestor genome may make different transcript variants in different primate species. Examination of the HERV-W elementrevealed that env fragments were detected on human chromosomes 1, 3-7, 12, 14, 17, 20, and X, whilst the pol fragments were detected on human chromosomes 2-8, 10-15, 20, 21, X, and Y. Bioinformatic blast search showed that almost full-length of the HERV-W family was identified on human chromosomes 1-8, 11-15, 17, 18, 21, and X. Expression analysis of HERV-W genes (gag, pol, and env) in human tissues by RT-PCR indicated that gag and pol were expressed in specific tissues, whilst env was constituitively expressed in all tissues examined. DNA sequence based phylogenetic analysis indicated that the gag, pol and env genes have evolved independently during primate evolution. It will thus be of considerable interest to expand the current HERV gene information of various primates and disease tissues.
Base Sequence
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Chromosomes, Human
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Endogenous Retroviruses
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Genes, env
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Genome
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Genome, Human
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Humans*
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Phylogeny
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Platyrrhini
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Polymerase Chain Reaction
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Polymorphism, Genetic
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Primates
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Retroelements*
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Zidovudine
3.Migration of Photoreceptor Cells Into the Subretinal Space in Rabbit Retina.
Journal of the Korean Ophthalmological Society 1991;32(2):174-179
The migration of photoreceptors into the subretinal space has been reported to occur in developing and aged rat retina, in aged human retina, in detached owl monkey, and in detached cat retina. Subretinal photoreceptor cells have been observed in aphakic-vitrectomized rabbit eyes with or without intravitreal saline or antibiotic injection. Variety of photoreceptor cell nuclei can be distinguished. The nuclei of photoreceptor cells change their shape so as to pass easily through the juncition and thereafter they returned to their original shape in sub retinal space. The mechanisms and biological significance of this phenomenon are not yet certain, but it may by one of the important factors contributing to decreased vision with aging.
Aging
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Animals
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Aotidae
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Cats
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Humans
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Photoreceptor Cells*
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Rats
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Retina*
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Retinaldehyde
4.Optical imaging of nociception in primary somatosensory cortex of non-human primates.
Li-Min CHEN ; Robert M FRIEDMAN ; Anna W ROE
Acta Physiologica Sinica 2008;60(5):664-668
While the activation of primary somatosensory (SI) cortex during pain perception is consistently reported in functional imaging studies on normal subjects and chronic pain patients, the specific roles of SI, particularly the subregions within SI, in the processing of sensory aspects of pain are still largely unknown. Using optical imaging of intrinsic signal (OIS) and single unit electrophysiology, we studied cortical activation patterns within SI cortex (among Brodmann areas 3a, 3b and 1) and signal amplitude changes to various intensities of non-nociceptive, thermal nociceptive and mechanical nociceptive stimulation of individual distal finerpads in anesthetized squirrel monkeys. We have demonstrated that areas 3a and 1 are preferentially involved in the processing of nociceptive information while areas 3b and 1 are preferentially activated in the processing of non-nociceptive (touch) information. Nociceptive activations of individual fingerpad were organized topographically suggesting that nociceptive topographic map exits in areas 3a and 1. Signal amplitude was enhanced to increasing intensity of mechanical nociceptive stimuli in areas 3a, 3b and 1. Within area 1, nociceptive response co-localizes with the non-nociceptive response. Therefore, we hypothesize that nocicepitve information is area-specifically represented within SI cortex, in which nociceptive inputs are preferentially represented in areas 3a and 1 while non-nociceptive inputs are preferentially represented in areas 3b and 1.
Animals
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Brain Mapping
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Nociception
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physiology
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Pain
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Saimiri
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Somatosensory Cortex
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physiology
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Touch
5.Induction of Anxiety-Like Phenotypes by Knockdown of Cannabinoid Type-1 Receptors in the Amygdala of Marmosets.
Lin ZHU ; Di ZHENG ; Rui LI ; Chen-Jie SHEN ; Ruolan CAI ; Chenfei LYU ; Binliang TANG ; Hao SUN ; Xiaohui WANG ; Yu DING ; Bin XU ; Guoqiang JIA ; Xinjian LI ; Lixia GAO ; Xiao-Ming LI
Neuroscience Bulletin 2023;39(11):1669-1682
The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases, such as depression and anxiety. Meanwhile, the endocannabinoid system plays a crucial role in regulating emotions and mainly functions through the cannabinoid type-1 receptor (CB1R), which is strongly expressed in the amygdala of non-human primates (NHPs). However, it remains largely unknown how the CB1Rs in the amygdala of NHPs regulate mental diseases. Here, we investigated the role of CB1R by knocking down the cannabinoid receptor 1 (CNR1) gene encoding CB1R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA. We found that CB1R knockdown in the amygdala induced anxiety-like behaviors, including disrupted night sleep, agitated psychomotor activity in new environments, and reduced social desire. Moreover, marmosets with CB1R-knockdown had up-regulated plasma cortisol levels. These results indicate that the knockdown of CB1Rs in the amygdala induces anxiety-like behaviors in marmosets, and this may be the mechanism underlying the regulation of anxiety by CB1Rs in the amygdala of NHPs.
Animals
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Callithrix
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Receptors, Cannabinoid
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Anxiety
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Amygdala
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Cannabinoids
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Phenotype
7.Immunocytochemical Study on the Monoaminergic Innervation of Diencephalic Visual Structures in the Squirrel Monkey.
Journal of the Korean Ophthalmological Society 1996;37(4):643-655
This study was for investigating relations between distributions of monoamines-norepinephrine, serotonin, and dopamine-on the visual system and their functions. Distributions of these monoamines in the lateral geniculate body, pulvinar, lateral posterior nucleus, and suprachiasmatic nucleus were investigated. Brain of a squirrel monkey was removed and frozen sectioned. Immunocytochemical study was performed for the tissue of the brain. Results showed that the anterior part of the lateral geniculate body contained more monoamines than the posterior part. More serotonins were distrbuted at the magnocellular part, and more dopamines were found at the parvocellular part. In pulvinar, more norepinephrines were distributed at the medial part, while serotonins were evenly distributed at all parts. In lateral posterior nucleus and suprachiasmatic nucleus, three kinds of monoamines were distributed with high density. Among the three, density of the serotonin showed the highest value. The lateral geniculate body relates with visual perception such as visual acuity, form and color perception, and stereopsis, while the pulvinar relates with visual functions, such as visual attention, sensory integration, and differentiation. Since norepinephrine and serotonine are distributed with high density in the pulvinar than in the lateral geniculate body those two monoamines are expected to playa major role for visual functions. Inferior part of the pulvinar relates with visual imagination, and the lateral posterior nucleus relates with integration of visual sensory. Relatively high distribution of dopamine in these two parts means that dopamine may playa major role for visual imagination and integration. As suprachiasmatic nucleus relates with controlling biorhythm, dense distribution of monoamines in suprachiasmatic nucleus implies that the monoamines may work for controlling biorhythm.
Brain
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Color Perception
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Depth Perception
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Dopamine
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Geniculate Bodies
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Imagination
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Lateral Thalamic Nuclei
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Norepinephrine
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Periodicity
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Pulvinar
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Saimiri*
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Sciuridae*
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Serotonin
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Suprachiasmatic Nucleus
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Visual Acuity
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Visual Perception
8.Immunolocalization of Aquaporin Water Channels in the Kidney of the Common Marmoset Monkey (Callithrix jacchus).
Korean Journal of Anatomy 2007;40(3):251-258
Aquaporin (AQP) is a water channel protein that is of critical importance in the urinary concentrating process and the regulation of water balance in the kidney, and at least seven AQPs are expressed at distinct sites in the kidney. The common marmoset monkey is widely used as an experimental animal included in the primate order in the filed of renal system. However, nothing is known about the expression AQP in the common marmoset monkey kidney. The purpose of this study was to establish the distribution of AQP-1, AQP-2, AQP-3 and AQP-4 in the common marmoset monkey kidney. We used three male common marmoset monkeys (Callithrix jacchus) ranging in age from 2 to 3 years. AQP-1 was expressed in segments 1, 2 and 3 of the proximal tubule, particularly abundant in segment 1, and also observed in the descending thin limb of the medulla. AQP-2 immunoreactivity was observed in the apical plasma membrane of principal cells in the cortical and medullary collecting ducts. AQP-3 immunostaining was intense in the basolateral plasma membrane of connecting tubules as well as in the cortical and outer medullary collecting ducts. AQP-4 was expressed mainly in the cytoplasm of inner medullary collecting duct cells. These data suggest that AQPs of the common marmoset monkey kidney may play a similar role in urinary concentrating processes and the regulation of water balance to that of AQPs in rats, mice and humans.
Animals
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Aquaporins*
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Callithrix*
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Cell Membrane
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Cytoplasm
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Extremities
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Haplorhini*
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Humans
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Immunohistochemistry
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Kidney*
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Male
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Mice
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Primates
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Rats
9.Experimental model of facial paralysis by nerve compression in primates (Callithrix sp.): A new model of facial paralysis in small nonhuman primates.
Felipe Costa NEIVA ; Andrei BORIN ; Simone CININI ; Luiz Eugênio A M MELLO ; Oswaldo Laércio CRUZ ; José Ricardo G TESTA
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2013;27(8):429-431
10.Detection of neutralizing antibody to human adenovirus type 5 in marmosets.
Ya-Chun SUN ; Ting-Ting LI ; Yi-Lin WANG ; Ling ZHANG ; Hai ZHU ; Cheng-Yao LI
Journal of Southern Medical University 2016;36(4):582-587
OBJECTIVETo construct a recombinant human adenovirus type 5 (Ad5) expressing luciferase and GFP reporter gene and detect neutralizing antibodies against adenovirus type 5 in common marmosets (Callithrix jacchus) to provide basic laboratory data for evaluating adenovirus vaccines.
METHODSLuciferase and GFP reporter genes from plasmid pHAGE-CMV-GFP were inserted into pDC315 to construct the recombinant adenovirus shutter plasmid pDC315-Luc-GFP. The shutter plasmid was co-transduced with pBHGlox(delta)E1,3Cre in 293A cell line to package the recombinant adenovirus rAd5/Luc/GFP. Three rounds of plaque formation experiment were performed to select the monoclonal adenovirus followed by purification with cesium chloride density gradient centrifugation and virus titration with TCID50 method. Chemiluminescence assay and flow cytometry were employed to detect the neutralizing antibody levels in 14 common marmosets.
RESULTSThe shuttle plasmid pDC315-Luc-GFP was successfully constructed and the recombinant adenovirus rAd5/Luc/GFP was packaged with a the titer reaching 6.9×10(11.5) PFU/mL. In the 14 marmosets, chemiluminescence assay identified 4 (28.6%) marmosets that were positive for Ad5-neutralizing antibodies, including 2 with a antibody titer of 1/16 and another 2 with a titer of 1/32; flow cytomery detected Ad5-neutralizing antibodies in 3 marmosets at the titer of 1/16.
CONCLUSIONChemiluminescence assay is a simple, sensitive, and accurate modality for detecting Ad5-neutralizing antibodies. Common marmosets have a very low positivity rate for Ad5-neutralizing antibodies and are therefore promising models for studying adenovirus-based vaccines and therapies.
Adenoviruses, Human ; immunology ; Animals ; Antibodies, Neutralizing ; blood ; Antibodies, Viral ; blood ; Callithrix ; Cell Line ; Humans ; Immunity, Humoral ; Luciferases ; Plasmids