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Looking at Developmental Neurotoxicity Testing from the Perspective of an Invertebrate Embryo
Developmental neurotoxicity (DNT) of chemical compounds disrupts the formation of a normal brain. There is impressive progress in the development of alternative testing methods for DNT potential in chemicals, some of which also incorporate invertebrate animals. This review briefly touches upon studi...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836978/ https://www.ncbi.nlm.nih.gov/pubmed/35163796 http://dx.doi.org/10.3390/ijms23031871 |
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author | Bicker, Gerd |
author_facet | Bicker, Gerd |
author_sort | Bicker, Gerd |
collection | PubMed |
description | Developmental neurotoxicity (DNT) of chemical compounds disrupts the formation of a normal brain. There is impressive progress in the development of alternative testing methods for DNT potential in chemicals, some of which also incorporate invertebrate animals. This review briefly touches upon studies on the genetically tractable model organisms of Caenorhabditis elegans and Drosophila melanogaster about the action of specific developmental neurotoxicants. The formation of a functional nervous system requires precisely timed axonal pathfinding to the correct cellular targets. To address this complex key event, our lab developed an alternative assay using a serum-free culture of intact locust embryos. The first neural pathways in the leg of embryonic locusts are established by a pair of afferent pioneer neurons which use guidance cues from membrane-bound and diffusible semaphorin proteins. In a systematic approach according to recommendations for alternative testing, the embryo assay quantifies defects in pioneer navigation after exposure to a panel of recognized test compounds for DNT. The outcome indicates a high predictability for test-compound classification. Since the pyramidal neurons of the mammalian cortex also use a semaphorin gradient for neurite guidance, the assay is based on evolutionary conserved cellular mechanisms, supporting its relevance for cortical development. |
format | Online Article Text |
id | pubmed-8836978 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88369782022-02-12 Looking at Developmental Neurotoxicity Testing from the Perspective of an Invertebrate Embryo Bicker, Gerd Int J Mol Sci Review Developmental neurotoxicity (DNT) of chemical compounds disrupts the formation of a normal brain. There is impressive progress in the development of alternative testing methods for DNT potential in chemicals, some of which also incorporate invertebrate animals. This review briefly touches upon studies on the genetically tractable model organisms of Caenorhabditis elegans and Drosophila melanogaster about the action of specific developmental neurotoxicants. The formation of a functional nervous system requires precisely timed axonal pathfinding to the correct cellular targets. To address this complex key event, our lab developed an alternative assay using a serum-free culture of intact locust embryos. The first neural pathways in the leg of embryonic locusts are established by a pair of afferent pioneer neurons which use guidance cues from membrane-bound and diffusible semaphorin proteins. In a systematic approach according to recommendations for alternative testing, the embryo assay quantifies defects in pioneer navigation after exposure to a panel of recognized test compounds for DNT. The outcome indicates a high predictability for test-compound classification. Since the pyramidal neurons of the mammalian cortex also use a semaphorin gradient for neurite guidance, the assay is based on evolutionary conserved cellular mechanisms, supporting its relevance for cortical development. MDPI 2022-02-07 /pmc/articles/PMC8836978/ /pubmed/35163796 http://dx.doi.org/10.3390/ijms23031871 Text en © 2022 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Bicker, Gerd Looking at Developmental Neurotoxicity Testing from the Perspective of an Invertebrate Embryo |
title | Looking at Developmental Neurotoxicity Testing from the Perspective of an Invertebrate Embryo |
title_full | Looking at Developmental Neurotoxicity Testing from the Perspective of an Invertebrate Embryo |
title_fullStr | Looking at Developmental Neurotoxicity Testing from the Perspective of an Invertebrate Embryo |
title_full_unstemmed | Looking at Developmental Neurotoxicity Testing from the Perspective of an Invertebrate Embryo |
title_short | Looking at Developmental Neurotoxicity Testing from the Perspective of an Invertebrate Embryo |
title_sort | looking at developmental neurotoxicity testing from the perspective of an invertebrate embryo |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836978/ https://www.ncbi.nlm.nih.gov/pubmed/35163796 http://dx.doi.org/10.3390/ijms23031871 |
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