(1/7) Immune disturbances during development increase susceptibility to neurodevelopmental disorders – but how? Work led by
@Jin_Cui_
& out today in
@Dev_Cell
reveals how the choroid plexus propagates maternal inflammatory signals into the fetal brain.🧠
(2/7) Using a mouse Maternal Immune Activation model, we uncover a broad inflammatory response in developing brain that manifests as a macrophage accumulation at the ChP and an increase in pro-inflammatory CSF cytokines. This response resembles the profile of CSF in ASD patients.
(3/7) We developed live imaging and analysis approaches for monitoring ChP macrophage behaviors in vivo in the embryonic brain, revealing incredible motility and mobility of these cells already very early on! Check out some example cells (green)(VIDEO).
(4/7) We also show that CCL2 acts by weakening the ChP barrier and recruits immune cells through anatomically distinct “hotspots” for immune cell entry into the brain at the tips of ChP villi, like those seen here:
(5/7) Elevated CCL2 produced by ChP and secreted into the CSF can ultimately disrupt cerebral cortical development. Considered with other work, these findings support CCL2 and ChP as contributors to pathologies associated with neurodevelopmental diseases.
(6/7) We hope that our findings of ChP-CSF inflammation will spark new hypotheses aimed at barrier protection for preventing neurodevelopmental disorders.