A distinctive subset of microglia positioned at the paraventricular zone are dedicated to cleaning the cerebrospinal fluid

Abstract

The interconnected ventricles in the central nervous system are filled with cerebrospinal fluid (CSF) which serves multifaceted roles including bring away metabolic wastes. However, whether there is an inherent "dislodging" mechanism, in addition to CSF drainage and reabsorption, at play for the removal of microparticles in the CSF is unclear. In this study, we identified a subset of microglia distributed in close proximity to the ependymal wall of ventricles. They differed from parenchymal microglia in morphology, behaviors and transcriptomes. In particular, the paraventricular microglia extended transependymal dendrites into the lumen of ventricles and were proficient in sequestering and phagocytosing intraventricular exogenous particles when present. A specific removal of the paraventricular microglia led to an acute ventriculomegaly due to an increased colloid osmotic pressure in the CSF resulting from protein accumulation. Thus, we identified the paraventricular microglia as specific guardians in monitoring and cleaning the CSF.