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

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 au...

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Published inDevelopmental neuroscience Vol. 45; no. 3; pp. 115 - 125
Main Authors Sasaki, Marie, Mitsuhashi, Takayuki, Goto, Fumiko, Shibata, Shinsuke, Kubo, Ken-ichiro, Oku, Shinju, Owashi, Akihiro, Takahashi, Takao
Format Journal Article
LanguageEnglish
Published Basel, Switzerland 01.06.2023
Subjects
In Tribute to Verne S. Caviness, Jr.: Research Article
Neuronogenesis
Child neurology
Neural stem cell
Cell cycle
Cytokine
Developing brain
Maternal inflammation
Neocortex
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Summary: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.
ISSN:0378-5866
1421-9859
DOI:10.1159/000529317