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Novel strategy of MPTP administration for stable parkinsonian symptoms in non-human primates
Jincheol Seo,Youngjeon Lee,Hyeon-Gu Yeo,Chang-Yeop Jeon,Kang-Jin Jeong,Seung-Ho Paik,Philyong Kang,Sangil Lee,Yujin Ahn,Jung-Joo Hong,Yeung Bae Jin,Bon-Sang Koo,Yeonghoon Son,Sang-Rae Lee,Kyu-Tae Chan 한국실험동물학회 2017 한국실험동물학회 학술발표대회 논문집 Vol.2017 No.2
박준형,서진철,원진영,Hyeon-Gu Yeo,안유진,Keonwoo Kim,진영배,구본상,임경섭,Kang-Jin Jeong,Philyong Kang,Hwal-Yong Lee,Seung Ho Baek,Chang-Yeop Jeon,홍정주,허재원,김영현,Sang-Je Park,김선욱,이동석,이상래,이영전 한국뇌신경과학회 2019 Experimental Neurobiology Vol.28 No.3
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.
In vivo study of paraspinal muscle weakness using botulinum toxin in one primate model
Han, Sang Kuy,Lee, Youngjeon,Hong, Jung-Joo,Yeo, Hyeon-Gu,Seo, Jincheol,Jeon, Chang-Yeop,Jeong, Kang-Jin,Jin, Yeung Bae,Kang, Philyong,Lee, Sangil,Shin, Choongsoo S.,Kim, Young Eun,Chun, Keyoung Jin,C Elsevier 2018 CLINICAL BIOMECHANICS -BRISTOL- Vol.53 No.-
<P><B>Abstract</B></P> <P><B>Background</B></P> <P>It has been generally speculated that paraspinal muscle weakness is related to the spinal degeneration including intervertebral disc failure. The purpose of this study was to investigate the effects of paraspinal muscle weakness induced by the botulinum toxin type-A on the lumbar spine and behavior pattern in an in-vivo primate model which has an upright locomotion similar to that of humans.</P> <P><B>Methods</B></P> <P>Botox injections into paraspinal muscle of one cynomolgus monkey were conducted biweekly up to 19 weeks at L2–L3, L3–L4 and L4–L5. MRIs were performed for measurement of muscle cross-sectional areas and behavioral data were collected using a high-resolution portable digital video camera.</P> <P><B>Findings</B></P> <P>The cross-sectional areas of the paraspinal muscles at L2–L3, L3–L4 and L4–L5 decreased by 8%, 12% and 8% at 21 weeks after the Botox injection, respectively. Intervertebral disc thickness at L2–L3, L3–L4 and L4–L5 decreased by 6%, 8% and 5% at 21 weeks after initial Botox injection, respectively. After the Botox injections, locomotion and movement activity of the monkey was decreased. The duration of sitting increased from 21% to a maximum of 97% at 9 weeks after the Botox injection, while stance time decreased from 9% to a minimum of 1% at 11 weeks post Botox injection.</P> <P><B>Interpretation</B></P> <P>The findings of this study revealed that paraspinal muscle atrophy affects intervertebral disc morphology and locomotion activity of a primate and may lead to an onset of intervertebral disc degeneration.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Botox injection produces paraspinal muscle atrophy in this primate model. </LI> <LI> Paraspinal muscle atrophy affects a loss of intervertebral disc thickness. </LI> <LI> Paraspinal muscle atrophy affects a locomotion activity of a primate. </LI> <LI> Locomotion activity was more static post compared to pre-Botox injections. </LI> </UL> </P>
Alu-Derived Alternative Splicing Events Specific to Macaca Lineages in CTSF Gene
Lee, Ja-Rang,Park, Sang-Je,Kim, Young-Hyun,Choe, Se-Hee,Cho, Hyeon-Mu,Lee, Sang-Rae,Kim, Sun-Uk,Kim, Ji-Su,Sim, Bo-Woong,Song, Bong-Seok,Jeong, Kang-Jin,Lee, Youngjeon,Jin, Yeung Bae,Kang, Philyong,Hu Korean Society for Molecular and Cellular Biology 2017 Molecules and cells Vol.40 No.2
Cathepsin F, which is encoded by CTSF, is a cysteine proteinase ubiquitously expressed in several tissues. In a previous study, novel transcripts of the CTSF gene were identified in the crab-eating monkey deriving from the integration of an Alu element-AluYRa1. The occurrence of AluYRa1-derived alternative transcripts and the mechanism of exonization events in the CTSF gene of human, rhesus monkey, and crabeating monkey were investigated using PCR and reverse transcription PCR on the genomic DNA and cDNA isolated from several tissues. Results demonstrated that AluYRa1 was only integrated into the genome of Macaca species and this lineage-specific integration led to exonization events by producing a conserved 3' splice site. Six transcript variants (V1-V6) were generated by alternative splicing (AS) events, including intron retention and alternative 5' splice sites in the 5' and 3' flanking regions of CTSF_AluYRa1. Among them, V3-V5 transcripts were ubiquitously expressed in all tissues of rhesus monkey and crab-eating monkey, whereas AluYRa1-exonized V1 was dominantly expressed in the testis of the crab-eating monkey, and V2 was only expressed in the testis of the two monkeys. These five transcript variants also had different amino acid sequences in the C-terminal region of CTSF, as compared to reference sequences. Thus, species-specific Alu-derived exonization by lineage-specific integration of Alu elements and AS events seems to have played an important role during primate evolution by producing transcript variants and gene diversification.
Jeong, Pil-Soo,Yoon, Seung-Bin,Choi, Seon-A,Song, Bong-Seok,Kim, Ji-Su,Sim, Bo-Woong,Park, Young-Ho,Yang, Hae-Jun,Mun, Seong-Eun,Kim, Young-Hyun,Kang, Philyong,Jeong, Kang-Jin,Lee, Youngjeon,Jin, Yeun CSIRO Publishing 2017 Reproduction, fertility, and development Vol.29 No.7
<P> Despite evidence of the presence of prostaglandin (PG) I2 in mammalian oviducts, its role in early development of in vitro-produced (IVP) embryos is largely unknown. Thus, in the present study we examined the effects of iloprost, a PGI2 analogue, on the in vitro developmental competence of early porcine embryos and the underlying mechanism(s). To examine the effects of iloprost on the development rate of IVF embryos, iloprost was added to the in vitro culture (IVC) medium and cultured for 6 days. Supplementation of the IVC medium with iloprost significantly improved developmental parameters, such as blastocyst formation rate, the trophectoderm : inner cell mass ratio and cell survival in IVF and parthenogenetically activated (PA) embryos. In addition, post-blastulation development into the expanded blastocyst stage was improved in iloprost-treated groups compared with controls. Interestingly, the phosphatidylinositol 3-kinase (PI3K)/AKT signalling pathway was significantly activated by iloprost supplementation in a concentration-dependent manner (10-1000 nM), and the beneficial effects of iloprost on the early development of porcine IVF and PA embryos was completely ablated by treatment with 2.5 μM wortmannin, a PI3K/AKT signalling inhibitor. Importantly, expression of the PI3K/AKT signalling pathway was significantly reduced in somatic cell nuclear transfer (SCNT) compared with IVF embryos, and iloprost supported the early development of SCNT embryos, as was the case for IVF and PA embryos, suggesting a consistent effect of iloprost on the IVC of IVP porcine embryos. Together, these results indicate that iloprost can be a useful IVC supplement for production of IVP early porcine embryos with high developmental competence. </P>