Intraventricular IL-17A administration activates microglia and alters their localization in the mouse embryo cerebral cortex.
Tetsuya SasakiSaki TomeYosuke TakeiPublished in: Molecular brain (2020)
Viral infection during pregnancy has been suggested to increase the probability of autism spectrum disorder (ASD) in offspring via the phenomenon of maternal immune activation (MIA). This has been modeled in rodents. Maternal T helper 17 cells and the effector cytokine, interleukin 17A (IL-17A), play a central role in MIA-induced behavioral abnormalities and cortical dysgenesis, termed cortical patch. However, it is unclear how IL-17A acts on fetal brain cells to cause ASD pathologies. To assess the effect of IL-17A on cortical development, we directly administered IL-17A into the lateral ventricles of the fetal mouse brain. We analyzed injected brains focusing on microglia, which express IL-17A receptors. We found that IL-17A activated microglia and altered their localization in the cerebral cortex. Our data indicate that IL-17A activates cortical microglia, which leads to a cascade of ASD-related brain pathologies, including excessive phagocytosis of neural progenitor cells in the ventricular zone.
Keyphrases
- autism spectrum disorder
- inflammatory response
- induced apoptosis
- functional connectivity
- heart failure
- intellectual disability
- immune response
- resting state
- neuropathic pain
- regulatory t cells
- pregnant women
- high fat diet
- multiple sclerosis
- subarachnoid hemorrhage
- metabolic syndrome
- cell cycle arrest
- minimally invasive
- white matter
- skeletal muscle
- high glucose
- big data
- electronic health record
- blood brain barrier
- artificial intelligence
- weight gain
- left ventricular
- pi k akt