1.Effect of Human or Mouse IL-7 on the Homeostasis of Porcine T Lymphocytes
Ji Hwa HONG ; Sang Hoon KIM ; Hyun Gyung KIM ; Jun Ho JANG ; Ryeo Gang SON ; Seung Pil PACK ; Young-Ho PARK ; Philyong KANG ; Kang-Jin JEONG ; Ji-Su KIM ; Hanbyeul CHOI ; Sun-Uk KIM ; Yong Woo JUNG
Immune Network 2021;21(3):e24-
Due to the inconsistent fluctuation of blood supply for transfusion, much attention has been paid to the development of artificial blood using other animals. Although mini-pigs are candidate animals, contamination of mini-pig T cells in artificial blood may cause a major safety concern. Therefore, it is important to analyze the cross-reactivity of IL-7, the major survival factor for T lymphocytes, between human, mouse, and mini-pig. Thus, we compared the protein sequences of IL-7 and found that porcine IL-7 was evolutionarily different from human IL-7. We also observed that when porcine T cells were cultured with either human or mouse IL-7, these cells did not increase the survival or proliferation compared to negative controls. These results suggest that porcine T cells do not recognize human or mouse IL-7 as their survival factor.
2.Effect of Human or Mouse IL-7 on the Homeostasis of Porcine T Lymphocytes
Ji Hwa HONG ; Sang Hoon KIM ; Hyun Gyung KIM ; Jun Ho JANG ; Ryeo Gang SON ; Seung Pil PACK ; Young-Ho PARK ; Philyong KANG ; Kang-Jin JEONG ; Ji-Su KIM ; Hanbyeul CHOI ; Sun-Uk KIM ; Yong Woo JUNG
Immune Network 2021;21(3):e24-
Due to the inconsistent fluctuation of blood supply for transfusion, much attention has been paid to the development of artificial blood using other animals. Although mini-pigs are candidate animals, contamination of mini-pig T cells in artificial blood may cause a major safety concern. Therefore, it is important to analyze the cross-reactivity of IL-7, the major survival factor for T lymphocytes, between human, mouse, and mini-pig. Thus, we compared the protein sequences of IL-7 and found that porcine IL-7 was evolutionarily different from human IL-7. We also observed that when porcine T cells were cultured with either human or mouse IL-7, these cells did not increase the survival or proliferation compared to negative controls. These results suggest that porcine T cells do not recognize human or mouse IL-7 as their survival factor.
3.Reference values of hematological and biochemical parameters in young-adult cynomolgus monkey (Macaca fascicularis) and rhesus monkey (Macaca mulatta) anesthetized with ketamine hydrochloride
Bon Sang KOO ; Dong Ho LEE ; Philyong KANG ; Kang Jin JEONG ; Sangil LEE ; Kijin KIM ; Youngjeon LEE ; Jae Won HUH ; Young Hyun KIM ; Sang Je PARK ; Yeung Bae JIN ; Sun Uk KIM ; Ji Su KIM ; Yeonghoon SON ; Sang Rae LEE
Laboratory Animal Research 2019;35(2):39-44
Nonhuman primate models are valuable in biomedical research. However, reference data for clinical pathology parameters in cynomolgus and rhesus monkeys are limited. In the present study, we established hematologic and biochemical reference intervals for healthy cynomolgus and rhesus monkeys anesthetized with ketamine hydrochloride. A total of 142 cynomolgus monkeys (28 males and 114 females) and 42 rhesus monkeys (22 males and 20 females) were selected and analyzed in order to examine reference intervals of 20 hematological and 16 biochemical parameters. The effects of sex were also investigated. Reference intervals for hematological and biochemical parameters were separately established by species (cynomolgus and rhesus) and sex (male and female). No sex-related differences were determined in erythrocyte-related parameters for cynomolgus and rhesus monkey housed in indoor laboratory conditions. Alkaline phosphatase and gamma glutamyltransferase were significantly lower in females than males in both cynomolgus and rhesus monkeys aged 48–96 months. The reference values for hematological and biochemical parameters established herein might provide valuable information for researchers using cynomolgus and rhesus monkeys in experimental conditions for biomedical studies.
4.Evaluation of fecal microbiomes associated with obesity in captive cynomolgus monkeys (Macaca fascicularis)
Bon Sang KOO ; Eun Ha HWANG ; Green KIM ; Hanseul OH ; Yeonghoon SON ; Dongho LEE ; Kyung Seob LIM ; Philyong KANG ; Sangil LEE ; Hwal Yong LEE ; Kang Jin JEONG ; Youngjeon LEE ; Seung Ho BAEK ; Chang Yeop JEON ; Sang Je PARK ; Young Hyun KIM ; Jae Won HUH ; Yeung Bae JIN ; Sun Uk KIM ; Sang Rae LEE ; Jung Joo HONG
Journal of Veterinary Science 2019;20(3):e19-
Microorganisms play important roles in obesity; however, the role of the gut microbiomes in obesity is controversial because of the inconsistent findings. This study investigated the gut microbiome communities in obese and lean groups of captive healthy cynomolgus monkeys reared under strict identical environmental conditions, including their diet. No significant differences in the relative abundance of Firmicutes, Bacteroidetes and Prevotella were observed between the obese and lean groups, but a significant difference in Spirochetes (p < 0.05) was noted. Microbial diversity and richness were similar, but highly variable results in microbial composition, diversity, and richness were observed in individuals, irrespective of their state of obesity. Distinct clustering between the groups was not observed by principal coordinate analysis using an unweighted pair group method. Higher sharedness values (95.81% ± 2.28% at the genus level, and 79.54% ± 5.88% at the species level) were identified among individual monkeys. This paper reports the association between the gut microbiome and obesity in captive non-human primate models reared under controlled environments. The relative proportion of Firmicutes and Bacteroidetes as well as the microbial diversity known to affect obesity were similar in the obese and lean groups of monkeys reared under identical conditions. Therefore, obesity-associated microbial changes reported previously appear to be associated directly with environmental factors, particularly diet, rather than obesity.
Bacteroidetes
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Diet
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Environment, Controlled
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Firmicutes
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Gastrointestinal Microbiome
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Haplorhini
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Macaca fascicularis
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Methods
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Microbiota
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Obesity
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Prevotella
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Primates
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Spirochaetales
5.Abnormal Mitochondria in a Non-human Primate Model of MPTP-induced Parkinson's Disease: Drp1 and CDK5/p25 Signaling
Junghyung PARK ; Jincheol SEO ; Jinyoung WON ; Hyeon Gu YEO ; Yu Jin AHN ; Keonwoo KIM ; Yeung Bae JIN ; Bon Sang KOO ; Kyung Seob LIM ; Kang Jin JEONG ; Philyong KANG ; Hwal Yong LEE ; Seung Ho BAEK ; Chang Yeop JEON ; Jung Joo HONG ; Jae Won HUH ; Young Hyun KIM ; Sang Je PARK ; Sun Uk KIM ; Dong Seok LEE ; Sang Rae LEE ; Youngjeon LEE
Experimental Neurobiology 2019;28(3):414-424
Mitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson's disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD. Here, we investigated the balance between mitochondrial fusion and fission in the substantia nigra of a non-human primate model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. We found that MPTP induced shorter and abnormally distributed mitochondria. This phenomenon was accompanied by the activation of dynamin-related protein 1 (Drp1), a mitochondrial fission protein, through increased phosphorylation at S616. Thereafter, we assessed for activation of the components of the cyclin-dependent kinase 5 (CDK5) and extracellular signal-regulated kinase (ERK) signaling cascades, which are known regulators of Drp1(S616) phosphorylation. MPTP induced an increase in p25 and p35, which are required for CDK5 activation. Together, these findings suggest that the phosphorylation of Drp1(S616) by CDK5 is involved in mitochondrial fission in the substantia nigra of a non-human primate model of MPTP-induced PD.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
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Cyclin-Dependent Kinase 5
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Cyclin-Dependent Kinases
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Dopaminergic Neurons
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Homeostasis
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Mitochondria
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Mitochondrial Dynamics
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Neurodegenerative Diseases
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Parkinson Disease
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Phosphorylation
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Phosphotransferases
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Primates
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Substantia Nigra
6.Increased CD68/TGFβ Co-expressing Microglia/Macrophages after Transient Middle Cerebral Artery Occlusion in Rhesus Monkeys
Hyeon Gu YEO ; Jung Joo HONG ; Youngjeon LEE ; Kyung Sik YI ; Chang Yeop JEON ; Junghyung PARK ; Jinyoung WON ; Jincheol SEO ; Yu Jin AHN ; Keonwoo KIM ; Seung Ho BAEK ; Eun Ha HWANG ; Green KIM ; Yeung Bae JIN ; Kang Jin JEONG ; Bon Sang KOO ; Philyong KANG ; Kyung Seob LIM ; Sun Uk KIM ; Jae Won HUH ; Young Hyun KIM ; Yeonghoon SON ; Ji Su KIM ; Chi Hoon CHOI ; Sang Hoon CHA ; Sang Rae LEE
Experimental Neurobiology 2019;28(4):458-473
The function of microglia/macrophages after ischemic stroke is poorly understood. This study examines the role of microglia/macrophages in the focal infarct area after transient middle cerebral artery occlusion (MCAO) in rhesus monkeys. We measured infarct volume and neurological function by magnetic resonance imaging (MRI) and non-human primate stroke scale (NHPSS), respectively, to assess temporal changes following MCAO. Activated phagocytic microglia/macrophages were examined by immunohistochemistry in post-mortem brains (n=6 MCAO, n=2 controls) at 3 and 24 hours (acute stage), 2 and 4 weeks (subacute stage), and 4, and 20 months (chronic stage) following MCAO. We found that the infarct volume progressively decreased between 1 and 4 weeks following MCAO, in parallel with the neurological recovery. Greater presence of cluster of differentiation 68 (CD68)-expressing microglia/macrophages was detected in the infarct lesion in the subacute and chronic stage, compared to the acute stage. Surprisingly, 98~99% of transforming growth factor beta (TGFβ) was found colocalized with CD68-expressing cells. CD68-expressing microglia/macrophages, rather than CD206⁺ cells, may exert anti-inflammatory effects by secreting TGFβ after the subacute stage of ischemic stroke. CD68⁺ microglia/macrophages can therefore be used as a potential therapeutic target.
Brain
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Haplorhini
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Immunohistochemistry
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Infarction, Middle Cerebral Artery
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Inflammation
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Macaca mulatta
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Magnetic Resonance Imaging
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Microglia
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Middle Cerebral Artery
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Primates
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Stroke
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Transforming Growth Factor beta
7.Impaired Hand Dexterity Function in a Non-human Primate Model with Chronic Parkinson’s Disease
Jin cheol SEO ; Jin young WON ; Keon woo KIM ; Jung hyung PARK ; Hyeon-Gu YEO ; Yu Gyeong KIM ; Seung Ho BAEK ; Hoonwon LEE ; Chang-Yeop JEON ; Won Seok CHOI ; Sangil LEE ; Ki Jin KIM ; Sung-Hyun PARK ; Yeong hoon SON ; Kang Jin JEONG ; Kyung Seob LIM ; Philyong KANG ; Hwal-Yong LEE ; Hee-Chang SON ; Jae-Won HUH ; Young-Hyun KIM ; Dong-Seok LEE ; Sang-Rae LEE ; Ji-Woong CHOI ; Young jeon LEE
Experimental Neurobiology 2020;29(5):376-388
ymptoms of Parkinson’s disease (PD) caused by loss of dopaminergic neurons are accompanied by movement disorders, including tremors, rigidity, bradykinesia, and akinesia. Non-human primate (NHP) models with PD play an essential role in the analysis of PD pathophysiology and behavior symptoms. As impairments of hand dexterity function can affect activities of daily living in patients with PD, research on hand dexterity function in NHP models with chronic PD is essential. Traditional rating scales previously used in the evaluation of animal spontaneous behavior were insufficient due to factors related to subjectivity and passivity. Thus, experimentally designed applications for an appropriate apparatus are necessary. In this study, we aimed to longitudinally assess hand dexterity function using hand dexterity task (HDT) in NHP-PD models. To validate this assessment, we analyzed the alteration in Parkinsonian tremor signs and the functionality of presynaptic dopaminergic neuron using positron emission tomography imaging of dopamine transporters in these models. In addition, a significant inverse correlation between HDT and DAT level was identified, but no local bias was found. The correlation with intention tremor signs was lower than the resting tremor. In conclusion, the evaluation of HDT may reflect behavioral symptoms of NHP-PD models. Furthermore, HDT was effectively used to experimentally distinguish intention tremors from other tremors.