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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Reactive microglia and mitochondrial unfolded protein response following ventriculomegaly and behavior defects in kaolin-induced hydrocephalus

  • Zhu, Jiebo (Department of Medical Science, Chungnam National University School of Medicine) ;
  • Lee, Min Joung (Department of Medical Science, Chungnam National University School of Medicine) ;
  • Chang, Hee Jin (Department of Medical Science, Chungnam National University School of Medicine) ;
  • Ju, Xianshu (Department of Medical Science, Chungnam National University School of Medicine) ;
  • Cui, Jianchen (Department of Medical Science, Chungnam National University School of Medicine) ;
  • Lee, Yu Lim (Department of Medical Science, Chungnam National University School of Medicine) ;
  • Go, Dahyun (Department of Medical Science, Chungnam National University School of Medicine) ;
  • Chung, Woosuk (Department of Medical Science, Chungnam National University School of Medicine) ;
  • Oh, Eungseok (Department of Medical Science, Chungnam National University School of Medicine) ;
  • Heo, Jun Young (Department of Medical Science, Chungnam National University School of Medicine)
  • Received : 2021.09.04
  • Accepted : 2021.12.04
  • Published : 2022.04.30
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Abstract

Ventriculomegaly induced by the abnormal accumulation of cerebrospinal fluid (CSF) leads to hydrocephalus, which is accompanied by neuroinflammation and mitochondrial oxidative stress. The mitochondrial stress activates mitochondrial unfolded protein response (UPRmt), which is essential for mitochondrial protein homeostasis. However, the association of inflammatory response and UPRmt in the pathogenesis of hydrocephalus is still unclear. To assess their relevance in the pathogenesis of hydrocephalus, we established a kaolin-induced hydrocephalus model in 8-week-old male C57BL/6J mice and evaluated it over time. We found that kaolin-injected mice showed prominent ventricular dilation, motor behavior defects at the 3-day, followed by the activation of microglia and UPRmt in the motor cortex at the 5-day. In addition, PARP-1/NF-κB signaling and apoptotic cell death appeared at the 5-day. Taken together, our findings demonstrate that activation of microglia and UPRmt occurs after hydrocephalic ventricular expansion and behavioral abnormalities which could be lead to apoptotic neuronal cell death, providing a new perspective on the pathogenic mechanism of hydrocephalus.

Keywords

Acknowledgement

This research was supported by the Ministry of Science, ICT (grant number NRF-2017R1A5A2015385, 2019M3E5D1A02068575, 2019R1F1A1059586).

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