Quantitative behavioural phenotyping to investigate anaesthesia induced neurobehavioural impairment

Abstract Anaesthesia exposure to the developing nervous system causes neuroapoptosis and behavioural impairment in vertebrate models. Mechanistic understanding is limited, and target-based approaches are challenging. High-throughput methods may be an important parallel approach to drug-discovery and...

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Autores principales:	Pratheeban Nambyiah, Andre E. X. Brown
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5d0198a2424b4539bba833f60a4f62e8
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spelling	oai:doaj.org-article:5d0198a2424b4539bba833f60a4f62e82021-12-02T17:37:40ZQuantitative behavioural phenotyping to investigate anaesthesia induced neurobehavioural impairment10.1038/s41598-021-98405-x2045-2322https://doaj.org/article/5d0198a2424b4539bba833f60a4f62e82021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98405-xhttps://doaj.org/toc/2045-2322Abstract Anaesthesia exposure to the developing nervous system causes neuroapoptosis and behavioural impairment in vertebrate models. Mechanistic understanding is limited, and target-based approaches are challenging. High-throughput methods may be an important parallel approach to drug-discovery and mechanistic research. The nematode worm Caenorhabditis elegans is an ideal candidate model. A rich subset of its behaviour can be studied, and hundreds of behavioural features can be quantified, then aggregated to yield a ‘signature’. Perturbation of this behavioural signature may provide a tool that can be used to quantify the effects of anaesthetic regimes, and act as an outcome marker for drug screening and molecular target research. Larval C. elegans were exposed to: isoflurane, ketamine, morphine, dexmedetomidine, and lithium (and combinations). Behaviour was recorded, and videos analysed with automated algorithms to extract behavioural features. Anaesthetic exposure during early development leads to persisting behavioural variation (in total, 125 features across exposure combinations). Higher concentrations, and combinations of isoflurane with ketamine, lead to persistent change in a greater number of features. Morphine and dexmedetomidine do not appear to lead to behavioural impairment. Lithium rescues the neurotoxic phenotype produced by isoflurane. Findings correlate well with vertebrate research: impairment is dependent on agent, is concentration-specific, is more likely with combination therapies, and can potentially be rescued by lithium. These results suggest that C. elegans may be an appropriate model with which to pursue phenotypic screens for drugs that mitigate the neurobehavioural impairment. Some possibilities are suggested for how high-throughput platforms might be organised in service of this field.Pratheeban NambyiahAndre E. X. BrownNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pratheeban Nambyiah Andre E. X. Brown Quantitative behavioural phenotyping to investigate anaesthesia induced neurobehavioural impairment
description	Abstract Anaesthesia exposure to the developing nervous system causes neuroapoptosis and behavioural impairment in vertebrate models. Mechanistic understanding is limited, and target-based approaches are challenging. High-throughput methods may be an important parallel approach to drug-discovery and mechanistic research. The nematode worm Caenorhabditis elegans is an ideal candidate model. A rich subset of its behaviour can be studied, and hundreds of behavioural features can be quantified, then aggregated to yield a ‘signature’. Perturbation of this behavioural signature may provide a tool that can be used to quantify the effects of anaesthetic regimes, and act as an outcome marker for drug screening and molecular target research. Larval C. elegans were exposed to: isoflurane, ketamine, morphine, dexmedetomidine, and lithium (and combinations). Behaviour was recorded, and videos analysed with automated algorithms to extract behavioural features. Anaesthetic exposure during early development leads to persisting behavioural variation (in total, 125 features across exposure combinations). Higher concentrations, and combinations of isoflurane with ketamine, lead to persistent change in a greater number of features. Morphine and dexmedetomidine do not appear to lead to behavioural impairment. Lithium rescues the neurotoxic phenotype produced by isoflurane. Findings correlate well with vertebrate research: impairment is dependent on agent, is concentration-specific, is more likely with combination therapies, and can potentially be rescued by lithium. These results suggest that C. elegans may be an appropriate model with which to pursue phenotypic screens for drugs that mitigate the neurobehavioural impairment. Some possibilities are suggested for how high-throughput platforms might be organised in service of this field.
format	article
author	Pratheeban Nambyiah Andre E. X. Brown
author_facet	Pratheeban Nambyiah Andre E. X. Brown
author_sort	Pratheeban Nambyiah
title	Quantitative behavioural phenotyping to investigate anaesthesia induced neurobehavioural impairment
title_short	Quantitative behavioural phenotyping to investigate anaesthesia induced neurobehavioural impairment
title_full	Quantitative behavioural phenotyping to investigate anaesthesia induced neurobehavioural impairment
title_fullStr	Quantitative behavioural phenotyping to investigate anaesthesia induced neurobehavioural impairment
title_full_unstemmed	Quantitative behavioural phenotyping to investigate anaesthesia induced neurobehavioural impairment
title_sort	quantitative behavioural phenotyping to investigate anaesthesia induced neurobehavioural impairment
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5d0198a2424b4539bba833f60a4f62e8
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Quantitative behavioural phenotyping to investigate anaesthesia induced neurobehavioural impairment

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