Maternal Immune Activation by Polyinosinic-Polycytidylic Acid Exposure Causes Cerebral Cortical Dysgenesis through Dysregulated Cell Cycle Kinetics of Neural Stem/Progenitor Cells

Marie Sasaki, Takayuki Mitsuhashi, Fumiko Goto, Shinsuke Shibata, Ken Ichiro Kubo, Shinju Oku, Akihiro Owashi, Takao Takahashi

Research output: Contribution to journalArticlepeer-review

Abstract

Maternal immune activation reportedly causes dysregulation of the cell cycle in stem cells and impairment of higher cortical function in rodents. Furthermore, in humans, maternal immune activation during the first to second trimester of pregnancy is strongly correlated with increased incidence of autism spectrum disorder in the offspring. Here, we show that in utero exposure to polyinosinic-polycytidylic acid (poly (I:C)) in mice during the early phase of neuronogenesis increases the probability of differentiation (quiescent fraction [Q fraction]) of neural stem/progenitor cells (NSPCs) without change in the length of cell cycle. This abnormal increase in the Q fraction is assumed to reduce the peak population size of NSPCs, resulting in the thinning of the neocortex in offspring because of the reduced production of neurons. Furthermore, the neocortex of poly (I:C)-exposed mice does not exhibit a layer-specific reduction in radial thickness, possibly because of increased apoptosis caused by poly (I:C) exposure during all stages of cortical development. These results suggest that maternal immune activation by poly (I:C) exposure may affect neocortical histogenesis by altering the cell cycle kinetics of NSPCs. In addition, the timing and amount of poly (I:C) exposure during pregnancy may have profound effects on cerebral cortical histogenesis.

Original languageEnglish
Pages (from-to)115-125
Number of pages11
JournalDevelopmental Neuroscience
Volume45
Issue number3
DOIs
Publication statusPublished - 2023 Jun 1

Keywords

  • Cell cycle
  • Child neurology
  • Cytokine
  • Developing brain
  • Maternal inflammation
  • Neocortex
  • Neural stem cell
  • Neuronogenesis

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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