CAESAREAN SECTION IMPACTS EARLY POSTNATAL CEREBELLAR DEVELOPMENT THROUGH BRAIN BARRIER MODULATION

Early life represents a critical window during which gut microbiota-derived signals shape brain development. Caesarean section (C-section) disrupts maternal microbial transmission at birth and is associated with altered immune signalling and behaviours, with potential impacts on neurodevelopmental trajectories. We recently identified early brain barrier dysfunction following C-section, particularly at the blood-cerebrospinal fluid (CSF) barrier of the lateral and third ventricle choroid plexuses (ChP), and to a lesser extent at the blood-brain barrier in the prefrontal cortex. The ChP is a key regulator of CSF composition and neurodevelopmental signalling. However, the fourth ventricle ChP remains largely unexplored, despite its proximity to the cerebellum, a brain region that undergoes extensive postnatal growth, displays marked sexual dimorphism, and contributes to motor, cognitive, and social behaviours. Here, we investigated whether alterations at the fourth ventricle ChP influence postnatal cerebellar development. Using a mouse model of C-section delivery, we assessed brain barrier integrity, cerebellar development, and immune-glial interactions at postnatal day 8. Barrier permeability was evaluated using tracer extravasation assays. Cerebellar neuronal populations (Purkinje and granule cells), glial cells (microglia and astrocytes), and ChP-associated macrophages were quantified by immunofluorescence and confocal microscopy. C-section delivery increased brain barrier permeability, with higher tracer fluorescence in the cerebellar region. This was associated with disrupted cerebellar cellular organisation and immune populations within the ChP. These findings identify the fourth ventricle ChP as a critical interface linking peripheral signals modulated by birth mode to cerebellar development and suggest that early barrier disruption may contribute to altered neurodevelopmental trajectories.