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

Tamar Licht, Esther Sasson, Batia Bell, Myriam Grunewald, Saran Kumar, Tirzah Kreisel, Ayal Ben-Zvi, Eli Keshet

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageAmerican English
Article numbere52134
Pages (from-to)1-20
Number of pages20
JournaleLife
Volume9
DOIs
StatePublished - Jun 2020

All Science Journal Classification (ASJC) codes

  • General Immunology and Microbiology
  • General Biochemistry,Genetics and Molecular Biology
  • General Neuroscience

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