Hippocampal neural stem cells facilitate access from circulation via apical cytoplasmic processes

Summary Blood vessels (BVs) are considered an integral component of neural stem cells (NSCs) niches. NSCs in the dentate gyrus (DG) have enigmatic elaborated apical cellular processes that are associated with BVs. Whether this contact serves as a mechanism for delivering circulating molecules is not known. Here we uncovered a previously unrecognized communication route allowing exclusive direct access of blood-borne substances to hippocampal NSCs in defiance of an intact blood-brain barrier (BBB). BBB-impermeable fluorescent tracer injected transcardially is selectively uptaken by DG NSCs within a minute, via the vessel-associated apical processes. These processes, measured >30nm in diameter, establish direct membrane-to-membrane contact with endothelial cells in areas devoid of the endothelial basement membrane. Doxorubicin, a brain-impermeable chemotherapeutic agent, is also readily and selectively uptaken by NSCs and reduces their proliferation, which might explain its problematic anti-neurogenic or cognitive side-effect. The newly-discovered NSC-BV communication route explains how circulatory neurogenic mediators are ‘sensed’ by NSCs.