Tremorgenic effects and functional metabolomics analysis of lolitrem B and its biosynthetic intermediates

Abstract The neuroactive mycotoxin lolitrem B causes a neurological syndrome in grazing livestock resulting in hyperexcitability, muscle tremors, ataxia and, in severe cases, clonic seizures and death. To define the effects of the major toxin lolitrem B in the brain, a functional metabolomic study w...

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Autores principales:	Priyanka Reddy, Simone Rochfort, Elizabeth Read, Myrna Deseo, Emily Jaehne, Maarten Van Den Buuse, Kathryn Guthridge, Martin Combs, German Spangenberg, Jane Quinn
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d9e45444ee0048c9a425345550819842
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spelling	oai:doaj.org-article:d9e45444ee0048c9a4253455508198422021-12-02T15:08:07ZTremorgenic effects and functional metabolomics analysis of lolitrem B and its biosynthetic intermediates10.1038/s41598-019-45170-72045-2322https://doaj.org/article/d9e45444ee0048c9a4253455508198422019-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-45170-7https://doaj.org/toc/2045-2322Abstract The neuroactive mycotoxin lolitrem B causes a neurological syndrome in grazing livestock resulting in hyperexcitability, muscle tremors, ataxia and, in severe cases, clonic seizures and death. To define the effects of the major toxin lolitrem B in the brain, a functional metabolomic study was undertaken in which motor coordination and tremor were quantified and metabolomic profiling undertaken to determine relative abundance of both toxin and key neurotransmitters in various brain regions in male mice. Marked differences were observed in the duration of tremor and coordination between lolitrem B pathway members, with some showing protracted effects and others none at all. Lolitrem B was identified in liver, kidney, cerebral cortex and thalamus but not in brainstem or cerebellum which were hypothesised previously to be the primary site of action. Metabolomic profiling showed significant variation in specific neurotransmitter and amino acid profiles over time. This study demonstrates accumulation of lolitrem B in the brain, with non-detectable levels of toxin in the brainstem and cerebellum, inducing alterations in metabolites such as tyrosine, suggesting a dynamic catecholaminergic response over time. Temporal characterisation of key pathways in the pathophysiological response of lolitrem B in the brain were also identified.Priyanka ReddySimone RochfortElizabeth ReadMyrna DeseoEmily JaehneMaarten Van Den BuuseKathryn GuthridgeMartin CombsGerman SpangenbergJane QuinnNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-17 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Priyanka Reddy Simone Rochfort Elizabeth Read Myrna Deseo Emily Jaehne Maarten Van Den Buuse Kathryn Guthridge Martin Combs German Spangenberg Jane Quinn Tremorgenic effects and functional metabolomics analysis of lolitrem B and its biosynthetic intermediates
description	Abstract The neuroactive mycotoxin lolitrem B causes a neurological syndrome in grazing livestock resulting in hyperexcitability, muscle tremors, ataxia and, in severe cases, clonic seizures and death. To define the effects of the major toxin lolitrem B in the brain, a functional metabolomic study was undertaken in which motor coordination and tremor were quantified and metabolomic profiling undertaken to determine relative abundance of both toxin and key neurotransmitters in various brain regions in male mice. Marked differences were observed in the duration of tremor and coordination between lolitrem B pathway members, with some showing protracted effects and others none at all. Lolitrem B was identified in liver, kidney, cerebral cortex and thalamus but not in brainstem or cerebellum which were hypothesised previously to be the primary site of action. Metabolomic profiling showed significant variation in specific neurotransmitter and amino acid profiles over time. This study demonstrates accumulation of lolitrem B in the brain, with non-detectable levels of toxin in the brainstem and cerebellum, inducing alterations in metabolites such as tyrosine, suggesting a dynamic catecholaminergic response over time. Temporal characterisation of key pathways in the pathophysiological response of lolitrem B in the brain were also identified.
format	article
author	Priyanka Reddy Simone Rochfort Elizabeth Read Myrna Deseo Emily Jaehne Maarten Van Den Buuse Kathryn Guthridge Martin Combs German Spangenberg Jane Quinn
author_facet	Priyanka Reddy Simone Rochfort Elizabeth Read Myrna Deseo Emily Jaehne Maarten Van Den Buuse Kathryn Guthridge Martin Combs German Spangenberg Jane Quinn
author_sort	Priyanka Reddy
title	Tremorgenic effects and functional metabolomics analysis of lolitrem B and its biosynthetic intermediates
title_short	Tremorgenic effects and functional metabolomics analysis of lolitrem B and its biosynthetic intermediates
title_full	Tremorgenic effects and functional metabolomics analysis of lolitrem B and its biosynthetic intermediates
title_fullStr	Tremorgenic effects and functional metabolomics analysis of lolitrem B and its biosynthetic intermediates
title_full_unstemmed	Tremorgenic effects and functional metabolomics analysis of lolitrem B and its biosynthetic intermediates
title_sort	tremorgenic effects and functional metabolomics analysis of lolitrem b and its biosynthetic intermediates
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/d9e45444ee0048c9a425345550819842
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Tremorgenic effects and functional metabolomics analysis of lolitrem B and its biosynthetic intermediates

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