Functional characterisation of the maturation of the blood-brain barrier in larval zebrafish.
Zebrafish are becoming increasingly popular as an organism in which to model human disease and to study the effects of small molecules on complex physiological and pathological processes. Since larvae are no more than a few millimetres in length, and can live in volumes as small as 100 microliters,...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3797749?pdf=render |
| _version_ | 1798046456962088960 |
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| author | Angeleen Fleming Heike Diekmann Paul Goldsmith |
| author_facet | Angeleen Fleming Heike Diekmann Paul Goldsmith |
| author_sort | Angeleen Fleming |
| collection | DOAJ |
| description | Zebrafish are becoming increasingly popular as an organism in which to model human disease and to study the effects of small molecules on complex physiological and pathological processes. Since larvae are no more than a few millimetres in length, and can live in volumes as small as 100 microliters, they are particularly amenable to high-throughput and high content compound screening in 96 well plate format. There is a growing literature providing evidence that many compounds show similar pharmacological effects in zebrafish as they do in mammals, and in particular humans. However, a major question regarding their utility for small molecule screening for neurological conditions is whether a molecule will reach its target site within the central nervous system. Studies have shown that Claudin-5 and ZO-1, tight-junction proteins which are essential for blood-brain barrier (BBB) integrity in mammals, can be detected in some cerebral vessels in zebrafish from 3 days post-fertilisation (d.p.f.) onwards and this timing coincides with the retention of dyes, immunoreactive tracers and fluorescent markers within some but not all cerebral vessels. Whilst these findings demonstrate that features of a BBB are first present at 3 d.p.f., it is not clear how quickly the zebrafish BBB matures or how closely the barrier resembles that of mammals. Here, we have combined anatomical analysis by transmission electron microscopy, functional investigation using fluorescent markers and compound uptake using liquid chromatography/tandem mass spectrometry to demonstrate that maturation of the zebrafish BBB occurs between 3 d.p.f. and 10 d.p.f. and that this barrier shares both structural and functional similarities with that of mammals. |
| first_indexed | 2024-04-11T23:37:54Z |
| format | Article |
| id | doaj.art-537680825c9f4e1581c9cc1aaea7e655 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-11T23:37:54Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-537680825c9f4e1581c9cc1aaea7e6552022-12-22T03:56:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7754810.1371/journal.pone.0077548Functional characterisation of the maturation of the blood-brain barrier in larval zebrafish.Angeleen FlemingHeike DiekmannPaul GoldsmithZebrafish are becoming increasingly popular as an organism in which to model human disease and to study the effects of small molecules on complex physiological and pathological processes. Since larvae are no more than a few millimetres in length, and can live in volumes as small as 100 microliters, they are particularly amenable to high-throughput and high content compound screening in 96 well plate format. There is a growing literature providing evidence that many compounds show similar pharmacological effects in zebrafish as they do in mammals, and in particular humans. However, a major question regarding their utility for small molecule screening for neurological conditions is whether a molecule will reach its target site within the central nervous system. Studies have shown that Claudin-5 and ZO-1, tight-junction proteins which are essential for blood-brain barrier (BBB) integrity in mammals, can be detected in some cerebral vessels in zebrafish from 3 days post-fertilisation (d.p.f.) onwards and this timing coincides with the retention of dyes, immunoreactive tracers and fluorescent markers within some but not all cerebral vessels. Whilst these findings demonstrate that features of a BBB are first present at 3 d.p.f., it is not clear how quickly the zebrafish BBB matures or how closely the barrier resembles that of mammals. Here, we have combined anatomical analysis by transmission electron microscopy, functional investigation using fluorescent markers and compound uptake using liquid chromatography/tandem mass spectrometry to demonstrate that maturation of the zebrafish BBB occurs between 3 d.p.f. and 10 d.p.f. and that this barrier shares both structural and functional similarities with that of mammals.http://europepmc.org/articles/PMC3797749?pdf=render |
| spellingShingle | Angeleen Fleming Heike Diekmann Paul Goldsmith Functional characterisation of the maturation of the blood-brain barrier in larval zebrafish. PLoS ONE |
| title | Functional characterisation of the maturation of the blood-brain barrier in larval zebrafish. |
| title_full | Functional characterisation of the maturation of the blood-brain barrier in larval zebrafish. |
| title_fullStr | Functional characterisation of the maturation of the blood-brain barrier in larval zebrafish. |
| title_full_unstemmed | Functional characterisation of the maturation of the blood-brain barrier in larval zebrafish. |
| title_short | Functional characterisation of the maturation of the blood-brain barrier in larval zebrafish. |
| title_sort | functional characterisation of the maturation of the blood brain barrier in larval zebrafish |
| url | http://europepmc.org/articles/PMC3797749?pdf=render |
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