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

• Published in: eLife Vol. 9
• Main Authors: Licht, Tamar, Sasson, Esther, Bell, Batia, Grunewald, Myriam, Kumar, Saran, Kreisel, Tirzah, Ben-Zvi, Ayal, Keshet, Eli
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 04.06.2020; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: adult neurogenesis; Animals; Antibiotics, Antineoplastic - metabolism; Basement Membrane - cytology; Basement Membrane - metabolism; Blood; Blood vessels; Blood-brain barrier; Blood-Brain Barrier - cytology; Blood-Brain Barrier - metabolism; Cell Communication; Cell division; Cell Surface Extensions - metabolism; Cell Surface Extensions - physiology; chemobrain; Cognitive ability; Cytoplasmic Vesicles - metabolism; Dentate gyrus; Doxorubicin; Doxorubicin - metabolism; Endothelial cells; Endothelial Cells - cytology; Endothelial Cells - metabolism; Endothelium; Female; Growth Substances - metabolism; Hippocampus; Hippocampus - cytology; Male; Mice; Microscopy; Neural stem cells; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Neural Stem Cells - physiology; Neurogenesis; Neuroscience; neurovascular unit; Stem cell transplantation; Stem cells; Stem Cells and Regenerative Medicine; adult neurogenesis; chemobrain; mouse; stem cells; dentate gyrus; blood-brain-barrier; neuroscience; regenerative medicine; neurovascular unit
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.52134

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. BBB-impermeable fluorescent tracer injected transcardially to mice is selectively uptaken by DG NSCs within a minute, via the vessel-associated apical processes. These processes, measured >30 nm in diameter, establish direct membrane-to-membrane contact with endothelial cells in specialized areas of irregular endothelial basement membrane and enriched with vesicular activity. 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.