PUBLICATION

Claudin-5a knockdown attenuates blood-neural barrier in zebrafish

Authors
Ahn, J.C., Hwang, S.J., Lee, H.J., Kim, K.W.
ID
ZDB-PUB-210910-13
Date
2021
Source
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP   250: 109176 (Journal)
Registered Authors
Keywords
Blood-brain barrier, Claudin-5, Tight junction, Zebrafish
MeSH Terms
  • Animals
  • Biological Transport
  • Blood-Brain Barrier/metabolism*
  • Blood-Brain Barrier/pathology
  • Brain/metabolism
  • Brain/pathology
  • Cerebral Ventricles/metabolism
  • Cerebral Ventricles/pathology
  • Claudin-5/antagonists & inhibitors*
  • Claudin-5/genetics
  • Claudin-5/metabolism
  • Morpholinos/pharmacology
  • Tight Junctions/metabolism
  • Tight Junctions/pathology
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/antagonists & inhibitors*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
34500089 Full text @ Comp. Biochem. Physiol. C Toxicol. Pharmacol.
Abstract
Mammalian claudin-5 (cldn5), a zebrafish cldn5a homolog, is essential to blood-brain barrier (BBB) integrity. Previously, the existence of an endothelial tight junction-based BBB with cldn5a expression in the cerebral microvessels was reported in zebrafish. However, the role of cldn5a in the cerebral microvessels of developing zebrafish has not been elucidated. Here, we further investigated the functional integrity of cldn5a in developing zebrafish by injecting cldn5a morpholinos. At 7 days post-fertilization, cldn5a immunoreactivity was detected on the brain surface, ventricular ependyma, and cerebral mircovessels but disappeared following cldna5a knockdown. Cldn5a morphants showed size-selective leakage of tracers through the BBB and downregulated expression of glucose transporter 1 (glut1) in the cerebral microvessels. In addition, leakiness in the blood-cerebrospinal fluid barrier was observed, implying the overall abnormal development of blood-neural barriers. The results of our study suggest that cldn5a is required for building and maintaining the blood-neural barrier during zebrafish development.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping