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

Mol Psychiatry. 2021 Jun;26(6):1808-1831. doi: 10.1038/s41380-020-0671-2. Epub 2020 Feb 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Brain
  • Disease Models, Animal
  • Female
  • Inflammation
  • Macrophage Colony-Stimulating Factor
  • Mice
  • Microglia*
  • Neurons
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor


  • Csf1r protein, mouse
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Macrophage Colony-Stimulating Factor