Hematopoietic monoamine oxidase A deficiency exacerbates neuroinflammation and demyelination in female but not male mice with experimental autoimmune encephalomyelitis.

Authors

Alessandro G Salerno, Amarylis C B A Wanschel, Giovana Y A Mascoli, Seonwook Kim, Elena Boudyguina, Reto Asmis

Published in

Frontiers in immunology. Volume 17. Pages 1829375. Epub Jun 30, 2026.

Abstract

Monoamine oxidase A (Mao A) is a mitochondrial enzyme responsible for the degradation of monoaminergic neurotransmitters. While pharmacological inhibition of Mao A has been reported to improve outcomes in experimental autoimmune encephalomyelitis (EAE), the role of Mao A in immune cells on disease progression was unknown.
To address this question, we generated mice with conditional Mao A deletion restricted to hematopoietic cells (Mao A_Leuko ^-/-), including circulating immune cells, and induced EAE by immunizing the mice with the MOG35-55 peptide. Disease severity, ataxia, inflammation, and demyelination were assessed.
Mao A_Leuko ^-/- female mice exhibited significantly accelerated weight loss, worsened ataxia, and a 2.2-fold increase in EAE severity compared with controls. Histological analyses revealed increased inflammation and enhanced demyelination in the lumbar spinal cords of Mao A_Leuko ^-/- mice. Immunohistochemistry revealed increased IBA-1⁺ and CD68⁺ staining in the spinal cord, consistent with enhanced microglia and macrophage accumulation and activation and exacerbated neuroinflammation. However, no differences in CD3⁺ T-cells levels were observed between female Mao A_Leuko ^-/- and Vav-i Cretg/wt EAE mice. These effects were restricted to female mice. No significant differences were observed in disease course or pathology between male Mao A_Leuko ^-/- and control mice. This study identified hematopoietic Mao A as a novel critical regulator of neuroimmune crosstalk, with loss of Mao A function exacerbating inflammation, demyelination, and neurological deficits in female but not male EAE mice.

PMID:
42454033
Bibliographic data and abstract were imported from PubMed on 15 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.