Functional and developmental analysis of the blood-brain barrier in zebrafish

Jae Yeon Jeong, Hyouk Bum Kwon, Jong Chan Ahn, Dongmin Kang, Seung Hae Kwon, Jeong Ae Park, Kyu Won Kim

Research output: Contribution to journalArticlepeer-review

320 Scopus citations

Abstract

The blood-brain barrier (BBB) is essential for maintaining brain homeostasis and protecting the brain from toxic substances. Breakdown of this barrier results in severe brain pathologies, whereas impermeability of the BBB is a major obstacle for drug delivery to the brain. Despite its importance, our understanding of the maturation and modulation of the BBB is limited. Zebrafish (Danio rerio) has emerged as a useful model organism for studying vertebrate development and disease mechanisms, as well as for preclinical drug screening. However, the nature of the BBB has not yet been examined in teleost fish. In this paper, we report that with the exception of the circumventricular organs, the cerebral microvessels in zebrafish are impermeable to sulfo-NHS-biotin and horseradish peroxidase (HRP). Brain endothelial cells show immunoreactivity to Claudin-5 and Zonula Occludens-1 (ZO-1), implying the presence of tight junctions in these cells. The expression of Claudin-5 and ZO-1 was detected in cerebral microvessels from 3 days post-fertilization (dpf), concomitant with maturation of the BBB, as determined by restricted permeability to HRP and various fluorescent tracers. Real-time analysis of fluorescent tracer leakage in embryonic zebrafish suggests that they may be used as an in vivo model for BBB breakdown. Taken together, our results show that the endothelial tight junction-based BBB of zebrafish is similar to that of higher vertebrates and thus, zebrafish may be an excellent genetic and experimental model organism for studying development and maintenance of the BBB.

Original languageEnglish
Pages (from-to)619-628
Number of pages10
JournalBrain Research Bulletin
Volume75
Issue number5
DOIs
StatePublished - 28 Mar 2008

Bibliographical note

Funding Information:
This work was supported by the Creative Research Initiatives (NeuroVascular Coordination Research Center) of the Ministry of Science and Technology, Korea. We would like to thank Yoon Kyung Choi and Hyo-Jong Lee for comments on Western blot analysis and providing HBEC cells.

Keywords

  • Circumventricular organ
  • Claudin-5
  • Endothelial
  • Tight junction
  • ZO-1

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