Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 박장환 | - |
dc.date.accessioned | 2021-01-13T02:20:30Z | - |
dc.date.available | 2021-01-13T02:20:30Z | - |
dc.date.issued | 2019-12 | - |
dc.identifier.citation | CELL DEATH & DISEASE, v. 10, article no. 943 | en_US |
dc.identifier.issn | 2041-4889 | - |
dc.identifier.uri | https://www.nature.com/articles/s41419-019-2174-0 | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/156939 | - |
dc.description.abstract | In the current study we present evidence suggesting that PARP-1 regulates neurogenesis and its deficiency may result in schizophrenia-like behavioral deficits in mice. PARP-1 knockout neural stem cells exhibited a marked upregulation of embryonic stem cell phosphatase that can suppress the proliferative signaling of PI3K-Akt and ERK. The suppressed activity of Akt and ERK in the absence of PARP-1 results in the elevation of FOXO1 activity and its downstream target genes p21 and p27, leading to the inhibition of neural stem cell proliferation. Moreover, expression of neurogenic factors and neuronal differentiation were decreased in the PARP-1 knockout neural stem cells whereas glial differentiation was increased. In accordance with the in vitro data, PARP-1 knockout mice exhibited reduced brain weight with enlarged ventricle as well as decreased adult neurogenesis in the hippocampus. Interestingly, PARP-1 knockout mice exhibited schizophrenia-like symptoms such as anxiety, depression, social interaction deficits, cognitive impairments, and prepulse inhibition deficits. Taken together, our results suggest that PARP-1 regulates neurogenesis during development and in adult and its absence may lead to the schizophrenia-like behavioral abnormality in mice. | en_US |
dc.description.sponsorship | This work was supported by grants from the National Research Foundation of Korea (2015R1D1A1A01059794, 2018R1A2B6003173, 2014R1A2A11050360, and 2017R1A2B4006991). ESP promoter-luciferase construct was kindly provided by Dr. Gerard Karsenty (Columbia University, USA). | en_US |
dc.language.iso | en | en_US |
dc.publisher | NATURE PUBLISHING GROUP | en_US |
dc.subject | PROGENITOR PROLIFERATION | en_US |
dc.subject | STEM-CELLS | en_US |
dc.subject | DISC1 | en_US |
dc.subject | MODULATION | en_US |
dc.subject | ACTIVATION | en_US |
dc.subject | BRAIN | en_US |
dc.subject | SUSCEPTIBILITY | en_US |
dc.subject | DEFICITS | en_US |
dc.subject | BIOLOGY | en_US |
dc.subject | LACKING | en_US |
dc.title | Defective neurogenesis and schizophrenia-like behavior in PARP-1-deficient mice | en_US |
dc.type | Article | en_US |
dc.relation.no | 12 | - |
dc.relation.volume | 10 | - |
dc.identifier.doi | 10.1038/s41419-019-2174-0 | - |
dc.relation.page | 943-958 | - |
dc.relation.journal | CELL DEATH & DISEASE | - |
dc.contributor.googleauthor | Hong, Seokheon | - |
dc.contributor.googleauthor | Yi, Jee Hyun | - |
dc.contributor.googleauthor | Lee, Soonje | - |
dc.contributor.googleauthor | Park, Chang-Hwan | - |
dc.contributor.googleauthor | Ryu, Jong Hoon | - |
dc.contributor.googleauthor | Shin, Ki Soon | - |
dc.contributor.googleauthor | Kang, Shin Jung | - |
dc.relation.code | 2019036142 | - |
dc.sector.campus | S | - |
dc.sector.daehak | GRADUATE SCHOOL OF BIOMEDICAL SCIENCE AND ENGINEERING[S] | - |
dc.sector.department | DEPARTMENT OF BIOMEDICAL SCIENCE | - |
dc.identifier.pid | chshpark | - |
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