Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Defective cell death of distinct microglial subsets contributes to ADHD-like behavior in mice

Hsiu-Chun Chuang, Eva K. Nichols, Isabella Rauch, Wei-Cheng Chang, Rhea Misra, Patrick M. Lin, Maiko Kitaoka, Russell E. Vance, Kaoru Saijo
doi: https://doi.org/10.1101/749390
Hsiu-Chun Chuang
1Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eva K. Nichols
1Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Isabella Rauch
1Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley
2Howard Hughes Medical Institute, University of California, Berkeley
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wei-Cheng Chang
1Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rhea Misra
1Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Patrick M. Lin
1Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maiko Kitaoka
1Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Russell E. Vance
1Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley
2Howard Hughes Medical Institute, University of California, Berkeley
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kaoru Saijo
1Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley
3Helen Wills Neuroscience Institute, University of California, Berkeley
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: ksaijo@berkeley.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Microglia are resident immune cells in the central nervous system that play essential roles to maintain homeostasis and neuronal function. Microglia are heterogeneous cells but the mechanisms by which they contribute to normal brain development remain unclear. Here,we show that microglia in the developing striatum and thalamus undergo pyroptosis,a type of lytic cell death that occurs as a result of Caspase-1 (CASP1) activation downstream of inflammasomes. We observe that pyroptosis occurs in a spatiotemporally regulated and Casp1-dependent manner during fetal brain development. Mice lacking Casp1 or the inflammasome regulating molecules, NLRP3, IL-1R, and Gasdermin D exhibit behavior changes characterized by hyperactivity, inattention, and impulsivity that are similar to attention-deficit/hyperactivity disorder (ADHD). Furthermore, re-expression of Casp1 in Cx3cr1+ cells including microglia restores normal behavior and cell death. We demonstrate that injection of an NLRP3 inhibitor into pregnant wild-type mice is sufficient to induce ADHD-like behaviors in offspring. These data suggest that microglial inflammasome activation and pyroptosis are essential for normal brain development and that genetic and pharmacological disruptions in this pathway may represent new ADHD risk factors.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted August 30, 2019.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Defective cell death of distinct microglial subsets contributes to ADHD-like behavior in mice
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Defective cell death of distinct microglial subsets contributes to ADHD-like behavior in mice
Hsiu-Chun Chuang, Eva K. Nichols, Isabella Rauch, Wei-Cheng Chang, Rhea Misra, Patrick M. Lin, Maiko Kitaoka, Russell E. Vance, Kaoru Saijo
bioRxiv 749390; doi: https://doi.org/10.1101/749390
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Defective cell death of distinct microglial subsets contributes to ADHD-like behavior in mice
Hsiu-Chun Chuang, Eva K. Nichols, Isabella Rauch, Wei-Cheng Chang, Rhea Misra, Patrick M. Lin, Maiko Kitaoka, Russell E. Vance, Kaoru Saijo
bioRxiv 749390; doi: https://doi.org/10.1101/749390

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (2530)
  • Biochemistry (4972)
  • Bioengineering (3482)
  • Bioinformatics (15212)
  • Biophysics (6897)
  • Cancer Biology (5390)
  • Cell Biology (7738)
  • Clinical Trials (138)
  • Developmental Biology (4530)
  • Ecology (7147)
  • Epidemiology (2059)
  • Evolutionary Biology (10227)
  • Genetics (7512)
  • Genomics (9786)
  • Immunology (4844)
  • Microbiology (13215)
  • Molecular Biology (5138)
  • Neuroscience (29435)
  • Paleontology (203)
  • Pathology (837)
  • Pharmacology and Toxicology (1463)
  • Physiology (2138)
  • Plant Biology (4748)
  • Scientific Communication and Education (1013)
  • Synthetic Biology (1338)
  • Systems Biology (4012)
  • Zoology (768)