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Article Dans Une Revue Molecular Psychiatry Année : 2020

Inhibition of colony stimulating factor 1 receptor corrects maternal inflammation-induced microglial and synaptic dysfunction and behavioral abnormalities

Hana Yeh
  • Fonction : Auteur
Jean-Christophe Delpech
Maya Woodbury
  • Fonction : Auteur
Alicia van Enoo
  • Fonction : Auteur
Zhi Ruan
  • Fonction : Auteur
Sudhir Sivakumaran
  • Fonction : Auteur
Yang You
  • Fonction : Auteur
Carl Holland
  • Fonction : Auteur
Teresa Guillamon-Vivancos
  • Fonction : Auteur
Asuka Yoshii-Kitahara
  • Fonction : Auteur
Mina Botros
  • Fonction : Auteur
Charlotte Madore
Pin-Hao Chao
  • Fonction : Auteur
Ankita Desani
  • Fonction : Auteur
Solaiappan Manimaran
  • Fonction : Auteur
Srinidhi Venkatesan Kalavai
  • Fonction : Auteur
W. Evan Johnson
  • Fonction : Auteur
Oleg Butovsky
  • Fonction : Auteur
Maria Medalla
  • Fonction : Auteur
Jennifer Luebke
  • Fonction : Auteur
Tsuneya Ikezu
  • Fonction : Auteur

Résumé

Abstract Maternal immune activation (MIA) disrupts the central innate immune system during a critical neurodevelopmental period. Microglia are primary innate immune cells in the brain although their direct influence on the MIA phenotype is largely unknown. Here we show that MIA alters microglial gene expression with upregulation of cellular protrusion/neuritogenic pathways, concurrently causing repetitive behavior, social deficits, and synaptic dysfunction to layer V intrinsically bursting pyramidal neurons in the prefrontal cortex of mice. MIA increases plastic dendritic spines of the intrinsically bursting neurons and their interaction with hyper-ramified microglia. Treating MIA offspring by colony stimulating factor 1 receptor inhibitors induces depletion and repopulation of microglia, and corrects protein expression of the newly identified MIA-associated neuritogenic molecules in microglia, which coalesces with correction of MIA-associated synaptic, neurophysiological, and behavioral abnormalities. Our study demonstrates that maternal immune insults perturb microglial phenotypes and influence neuronal functions throughout adulthood, and reveals a potent effect of colony stimulating factor 1 receptor inhibitors on the correction of MIA-associated microglial, synaptic, and neurobehavioral dysfunctions.

Dates et versions

hal-03259500 , version 1 (14-06-2021)

Identifiants

Citer

Seiko Ikezu, Hana Yeh, Jean-Christophe Delpech, Maya Woodbury, Alicia van Enoo, et al.. Inhibition of colony stimulating factor 1 receptor corrects maternal inflammation-induced microglial and synaptic dysfunction and behavioral abnormalities. Molecular Psychiatry, 2020, ⟨10.1038/s41380-020-0671-2⟩. ⟨hal-03259500⟩

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