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

Heejung Chun, Jiwoon Lim, Ki Duk Park, C. Justin Lee

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)354-367
Number of pages14
JournalGlia
Volume70
Issue number2
DOIs
Publication statusPublished - 2022 Feb

Bibliographical note

Funding Information:
This work was supported by the Institute for Basic Science (IBS), Center for Cognition and Sociality (IBS‐R001‐D2). We are grateful to Dr. Byoung Joo Gwag from GNT Pharma for providing crisdesalazine (AAD‐2004) and Dr. Ki Duk Park for providing KDS2010.

Publisher Copyright:
© 2021 Wiley Periodicals LLC.

All Science Journal Classification (ASJC) codes

  • Neurology
  • Cellular and Molecular Neuroscience

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