MicroRNA-124 contributes to neurogenesis through regulating its targets, but its expression both in the brain of Huntington's disease mouse models and patients is decreased. However, the effects of microRNA-124 on th...MicroRNA-124 contributes to neurogenesis through regulating its targets, but its expression both in the brain of Huntington's disease mouse models and patients is decreased. However, the effects of microRNA-124 on the progression of Huntington's disease have not been reported. Results from this study showed that microRNA-124 increased the latency to fall for each R6/2 Hunting- ton's disease transgenic mouse in the rotarod test. 5-Bromo-2'-deoxyuridine (BrdU) staining of the striatum shows an increase in neurogenesis. In addition, brain-derived neurotrophic factor and peroxisome proliferator-activated receptor gamma coactivator 1-alpha protein levels in the striatum were increased and SRY-related HMG box transcription factor 9 protein level was de- creased. These findings suggest that microRNA-124 slows down the progression of Huntington's disease possibly through its important role in neuronal differentiation and survival.展开更多
In this study, we induced cerebral infarction in rats by occluding the right middle cerebral artery, and tested the effects of electroacupuncture at the Baihui acupoint (DU 20). Motor and sensory function was tested...In this study, we induced cerebral infarction in rats by occluding the right middle cerebral artery, and tested the effects of electroacupuncture at the Baihui acupoint (DU 20). Motor and sensory function was tested using Garcia’s scale and motor weakness grading, and the expression of vascular endothelial growth factor in the brain was quantified using immunoblotting and immunohistochemistry. We found that scalp electroacupuncture at DU 20 significantly improved motor performance and sensory function in rats with stroke, and this was accompanied by an increased expression of vascular endothelial growth factor in the ischemic brain tissue and peri-ischemic area. In addition, Pearson correlation analysis showed that the improvements in functional recovery were correlated with the increased expression of vascular endothelial growth factor.展开更多
Human growth hormone(GH)is a single-chain polypeptide of 191 amino acids that is involved in the regulation of various physiological processes,such as growth and metabolism.GH is synthesized and secreted by somatotr...Human growth hormone(GH)is a single-chain polypeptide of 191 amino acids that is involved in the regulation of various physiological processes,such as growth and metabolism.GH is synthesized and secreted by somatotropic cells in the anterior pituitary gland.Its secretion is primarily regulated by a balance between growth hormone-releasing hormone and growth hormone-inhibiting hormone,展开更多
Background:MicroRNAs(miRNAs)are endogenous non-coding RNAS that regulate gene expression at the post-transcriptional level and are key modulators in neurodegenerative diseases.Overexpressed miRNAs play an important ro...Background:MicroRNAs(miRNAs)are endogenous non-coding RNAS that regulate gene expression at the post-transcriptional level and are key modulators in neurodegenerative diseases.Overexpressed miRNAs play an important role in amyotrophic lateral sclerosis(ALS);however,the pathogenic mechanisms of deregulated miRNAS are still unclear.Methods:We aimed to assess the dysfunction of RNAS or miRNAs in fALS(SOD1 mutations).We compared the RNA-seq of subcellular fractions in NSC-34 WT(hSOD1)and MT(hSOD1(G93A))cells to find altered RNAs or miRNAs.We identified that Hif1a and Mef2c were upregulated,and Mctp1 and Rarb were downregulated in the cytoplasm of NSC-34 MT cells.Results:SOD1 mutations decreased the level of miR-18b-5p.Induced Hif1a which is the target for miR-18b increased Mef2c expression as a transcription factor.Mef2c upregulated miR-206 as a transcription factor.Inhibition of Mctp1 and Rarb,which are targets of miR-206,induced intracellular Ca^2+ levels and reduced cell differentiation,respectively.The miR-18b-5p pathway was also observed in G93A Tg mice,fALS(G86S)patient,and iPSC-derived motor neurons from fALS(G17S)patient.Conclusions:Our data indicate that SOD1 mutation decreases miR-18b-5p,which sequentially regulates Hif1a,Mef2c,miR-206,Mctp1 and Rarb in fALS-linked SOD1 mutation.These results provide new insights into the downregulation of miR-18b-5p-dependent pathogenic mechanisms of ALS.展开更多
基金supported by a grant(A121911 and HI14C2348)of the Korean Health Technology R&D Project,Ministry of Health&WelfareNational Research Foundation of Korea(NRF)(2011-0012728 and 2014R1A2A1A11051520)
文摘MicroRNA-124 contributes to neurogenesis through regulating its targets, but its expression both in the brain of Huntington's disease mouse models and patients is decreased. However, the effects of microRNA-124 on the progression of Huntington's disease have not been reported. Results from this study showed that microRNA-124 increased the latency to fall for each R6/2 Hunting- ton's disease transgenic mouse in the rotarod test. 5-Bromo-2'-deoxyuridine (BrdU) staining of the striatum shows an increase in neurogenesis. In addition, brain-derived neurotrophic factor and peroxisome proliferator-activated receptor gamma coactivator 1-alpha protein levels in the striatum were increased and SRY-related HMG box transcription factor 9 protein level was de- creased. These findings suggest that microRNA-124 slows down the progression of Huntington's disease possibly through its important role in neuronal differentiation and survival.
基金the Incheon St. Mary’s Hospital of the Catholic University of Korea, through the Clinical Research Laboratory Foundation Program, Korea Health 21 R&D Project, No. A092058, and WCU Neurocytomics
文摘In this study, we induced cerebral infarction in rats by occluding the right middle cerebral artery, and tested the effects of electroacupuncture at the Baihui acupoint (DU 20). Motor and sensory function was tested using Garcia’s scale and motor weakness grading, and the expression of vascular endothelial growth factor in the brain was quantified using immunoblotting and immunohistochemistry. We found that scalp electroacupuncture at DU 20 significantly improved motor performance and sensory function in rats with stroke, and this was accompanied by an increased expression of vascular endothelial growth factor in the ischemic brain tissue and peri-ischemic area. In addition, Pearson correlation analysis showed that the improvements in functional recovery were correlated with the increased expression of vascular endothelial growth factor.
基金supported by grants from the Korea Health 21 R&D Project(HI14C2348)the National Research Foundation of Korea(NRF2014R1A2A1A11051520)
文摘Human growth hormone(GH)is a single-chain polypeptide of 191 amino acids that is involved in the regulation of various physiological processes,such as growth and metabolism.GH is synthesized and secreted by somatotropic cells in the anterior pituitary gland.Its secretion is primarily regulated by a balance between growth hormone-releasing hormone and growth hormone-inhibiting hormone,
基金This research was supported by the Brain Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT(2017M3C7A102536521 and 2018R1A5A202596413).
文摘Background:MicroRNAs(miRNAs)are endogenous non-coding RNAS that regulate gene expression at the post-transcriptional level and are key modulators in neurodegenerative diseases.Overexpressed miRNAs play an important role in amyotrophic lateral sclerosis(ALS);however,the pathogenic mechanisms of deregulated miRNAS are still unclear.Methods:We aimed to assess the dysfunction of RNAS or miRNAs in fALS(SOD1 mutations).We compared the RNA-seq of subcellular fractions in NSC-34 WT(hSOD1)and MT(hSOD1(G93A))cells to find altered RNAs or miRNAs.We identified that Hif1a and Mef2c were upregulated,and Mctp1 and Rarb were downregulated in the cytoplasm of NSC-34 MT cells.Results:SOD1 mutations decreased the level of miR-18b-5p.Induced Hif1a which is the target for miR-18b increased Mef2c expression as a transcription factor.Mef2c upregulated miR-206 as a transcription factor.Inhibition of Mctp1 and Rarb,which are targets of miR-206,induced intracellular Ca^2+ levels and reduced cell differentiation,respectively.The miR-18b-5p pathway was also observed in G93A Tg mice,fALS(G86S)patient,and iPSC-derived motor neurons from fALS(G17S)patient.Conclusions:Our data indicate that SOD1 mutation decreases miR-18b-5p,which sequentially regulates Hif1a,Mef2c,miR-206,Mctp1 and Rarb in fALS-linked SOD1 mutation.These results provide new insights into the downregulation of miR-18b-5p-dependent pathogenic mechanisms of ALS.