Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Minoxidil Regulates Aging-Like Phenotypes in Rat Cortical Astrocytes In Vitro

  • Minji, Bang (Biological Science, College of Science & Technology, Dankook University) ;
  • Seung Jin, Yang (Department of Life Science, Handong Global University) ;
  • TaeJin, Ahn (Department of Life Science, Handong Global University) ;
  • Seol-Heui, Han (Department of Neurology, Konkuk Hospital Medical Center) ;
  • Chan Young, Shin (Department of Neuroscience and Pharmacology, School of Medicine, Konkuk University) ;
  • Kyoung Ja, Kwon (Department of Neuroscience and Pharmacology, School of Medicine, Konkuk University)
  • Received : 2022.11.10
  • Accepted : 2022.11.25
  • Published : 2023.01.01
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Abstract

Mainly due to the slanted focus on the mechanism and regulation of neuronal aging, research on astrocyte aging and its modulation during brain aging is scarce. In this study, we established aged astrocyte culture model by long-term culturing. Cellular senescence was confirmed through SA-β-gal staining as well as through the examination of morphological, molecular, and functional markers. RNA sequencing and functional analysis of astrocytes were performed to further investigate the detailed characteristics of the aged astrocyte model. Along with aged phenotypes, decreased astrocytic proliferation, migration, mitochondrial energetic function and support for neuronal survival and differentiation has been observed in aged astrocytes. In addition, increased expression of cytokines and chemokine-related factors including plasminogen activator inhibitor -1 (PAI-1) was observed in aged astrocytes. Using the RNA sequencing results, we searched potential drugs that can normalize the dysregulated gene expression pattern observed in long-term cultured aged astrocytes. Among several candidates, minoxidil, a pyrimidine-derived anti-hypertensive and anti-pattern hair loss drug, normalized the increased number of SA-β-gal positive cells and nuclear size in aged astrocytes. In addition, minoxidil restored up-regulated activity of PAI-1 and increased mitochondrial superoxide production in aged astrocytes. We concluded that long term culture of astrocytes can be used as a reliable model for the study of astrocyte senescence and minoxidil can be a plausible candidate for the regulation of brain aging.

Keywords

Acknowledgement

This work was supported by the Brain Research Program (2019M3C7A1031455) and the Basic Science Research Program (2022R1A2C1005917) through the National Research Foundation (NRF) of Korea funded by the Ministry of Science, ICT & Future Planning, and the NRF grant funded by the Korea government (MSIT) (2016R1A5A2012284, 2017M3A9G2077568 and 2020M3E5D9080165).

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