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인지 및 사회성 연구단
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Inhibition of monoamine oxidase B prevents reactive astrogliosis and scar formation in stab wound injury model

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Title
Inhibition of monoamine oxidase B prevents reactive astrogliosis and scar formation in stab wound injury model
Author(s)
Heejung Chun; Jiwoon Lim; Park, Ki Duk; C. Justin Lee
Publication Date
2022-02
Journal
GLIA, v.70, no.2, pp.354 - 367
Publisher
John Wiley and Sons Inc
Abstract
© 2021 Wiley Periodicals LLC.Reactive astrocytes manifest molecular, structural, and functional alterations under various pathological conditions. We have previously demonstrated that the reactive astrocytes of the stab wound injury model (STAB) display aberrant cellular gamma-aminobutyric acid (GABA) content and tonic GABA release, whereas the active astrocytes under enriched environment (EE) express high levels of proBDNF. However, the role of monoamine oxidase B (MAO-B) in reactive astrogliosis and hypertrophy still remains unknown. Here, we investigate the role of MAO-B, a GABA-producing enzyme, in reactive astrogliosis in STAB. We observed that the genetic removal of MAO-B significantly reduced the hypertrophy, scar formation, and GABA production of reactive astrocytes, whereas the MAO-B overexpression under glial fibrillary acidic protein (GFAP) promoter enhanced the levels of GFAP and GABA. Furthermore, we found that one of the by-products of the MAO-B action, H2O2, but not GABA, was sufficient and necessary for the hypertrophy of reactive astrocytes. Notably, we identified two potent pharmacological tools to attenuate scar-forming astrogliosis—the recently developed reversible MAO-B inhibitor, KDS2010, and an H2O2 scavenger, crisdesalazine (AAD-2004). Our results implicate that inhibiting MAO-B activity has dual beneficial effects in preventing astrogliosis and scar-formation under brain injury, and that the MAO-B/H2O2 pathway can be a useful therapeutic target with a high clinical potential.
URI
https://pr.ibs.re.kr/handle/8788114/10836
DOI
10.1002/glia.24110
ISSN
0894-1491
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > 1. Journal Papers (저널논문)
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