Autoantibody profiling of monoamine oxidase A knockout mice, an autism spectrum disorder model

Guan-Da Syu; F X Reymond Sutandy; Kevin Chen; Yawei Cheng; Chien-Sheng Chen; Jean C Shih

doi:10.1016/j.bbi.2022.10.001

Autoantibody profiling of monoamine oxidase A knockout mice, an autism spectrum disorder model

Brain Behav Immun. 2023 Jan:107:193-200. doi: 10.1016/j.bbi.2022.10.001. Epub 2022 Oct 12.

Authors

Guan-Da Syu¹, F X Reymond Sutandy², Kevin Chen³, Yawei Cheng⁴, Chien-Sheng Chen⁵, Jean C Shih⁶

Affiliations

¹ Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, Tainan, Taiwan; International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwan; Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan. Electronic address: guanda@gs.ncku.edu.tw.
² Institute for Biochemistry II, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany.
³ Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, USA.
⁴ Department of Physical Medicine and Rehabilitation, National Yang-Ming University Hospital, Yilan, Taiwan; Institute of Neuroscience and Brain Research Center, National Yang-Ming University, Taipei, Taiwan; Department of Education and Research, Taipei City Hospital, Taipei, Taiwan.
⁵ Department of Food Safety/Hygiene and Risk Management, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC. Electronic address: cschen@gs.ncku.edu.tw.
⁶ Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, USA; USC-Taiwan Center for Translational Research, University of Southern California, Los Angeles, USA; Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, USA. Electronic address: jcshih@usc.edu.

PMID: 36243286
DOI: 10.1016/j.bbi.2022.10.001

Abstract

Monoamine oxidase A (MAO A) is the critical enzyme to degrade serotonin in the brain and the knockout mouse exhibits hyperserotonemia and abnormalities that are observed in autism spectrum disorder (ASD). Thus, the MAO A knockout mouse is a valuable model for studying neurological and behavioral impairments in ASD. Based on the immune dysfunction hypothesis, dysregulated humoral immunity may cause neurological impairments. To address this hypothesis, we use high-density proteome microarray to profile the serum antibodies in both wild-type and MAO A knockout mice. The distingue autoantibody signatures were observed in the MAO A knockout and wild-type controls and showed 165 up-regulated and 232 down-regulated autoantibodies. The up-regulated autoantibodies were prone to target brain tissues while down-regulated ones were enriched in sex organs. The identified autoantibodies help bridge the gap between ASD mouse models and humoral immunity, not only yielding insights into the pathological mechanisms but also providing potential biomarkers for translational research in ASD.

Keywords: Antibody profiling; Autism spectrum disorder (ASD); Human proteome microarrays; MAO A knockout mice; Monoamine oxidase A (MAO A); Serology; Serotonin.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autism Spectrum Disorder* / genetics
Autoantibodies
Mice
Mice, Knockout
Monoamine Oxidase* / genetics

Substances

Monoamine Oxidase
Autoantibodies

Grants and funding

R01 MH039085/MH/NIMH NIH HHS/United States