A functional metabolomics analysis of lolitrem B and its biosynthetic intermediates in the murine brain

Priyanka Reddy, Martin Combs, Elizabeth Read, Myrna Deseo, Emily Jaehne, Maarten Van Den Buuse, Kathryn Guthridge, German Spangenberg, Simone Rochfort, Jane Quinn

Research output: Other contribution to conferenceAbstract

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. Lolitrem B is the endpoint in a biosynthetic pathway of indole diterpenoid toxins present in fodder yet the neuroactive status of it’s pathways intermediates remains undefined. To define the effects of lolitrem B and it’s pathway intermediates terpendoles B, C and E in the brain, a functional metabolomic study was undertaken in which cordination and tremor were quantified and metabolomic profiling undertaken to determine quantification anad relative abundance of both toxin and key neurotransmitters in various brain regions. Marked differences were observed in the duration of tremor and coordination between pathway members, with some showing protracted effects and others none at all. Quantification of lolitrem B using LCMS/MS QQQ identified presence of Lolitrem B in liver and kidney, cerebral cortex, thalamus and brain stem but not in cerebellum. Metabolomic profiling by LCMS/MS-QToF of brain isolated from intoxicated animals using showed significnat variation in targetted neurotransmitter and amino acid profiles over time. This study demonstrates for the first time bioaccumulation of lolitrem B in the brain, with absence of detectable levels of toxin in the cerebellum, as determining a dynamic catecholenergic response over time. This data is indicates that the indole diterpenoid toxins induce alterations in catecholamine pathways in the brain as well identifying pathway intermediates with non-tremorgenic profiles. This study idetnfies a functional metabolomic approach for physiological profiling of neurotoxic agents in the brain.
Original languageEnglish
Pages18
Number of pages1
Publication statusPublished - 2018
Event10th International Symposium on Poisonous Plants : ISOPP 10 - Red Lion Conference Center, St George , United States
Duration: 16 Sep 201820 Sep 2018
https://conference.usu.edu/ISOPP/

Conference

Conference10th International Symposium on Poisonous Plants
CountryUnited States
CitySt George
Period16/09/1820/09/18
Internet address

Fingerprint

Metabolomics
Brain
Tremor
Diterpenes
Cerebellum
Neurotransmitter Agents
Kidney Cortex
Mycotoxins
Biosynthetic Pathways
Livestock
Ataxia
Thalamus
Cerebral Cortex
Brain Stem
Catecholamines
lolitrem B
Seizures
Amino Acids
Liver

Cite this

Reddy, P., Combs, M., Read, E., Deseo, M., Jaehne, E., Van Den Buuse, M., ... Quinn, J. (2018). A functional metabolomics analysis of lolitrem B and its biosynthetic intermediates in the murine brain. 18. Abstract from 10th International Symposium on Poisonous Plants , St George , United States.
Reddy, Priyanka ; Combs, Martin ; Read, Elizabeth ; Deseo, Myrna ; Jaehne, Emily ; Van Den Buuse, Maarten ; Guthridge, Kathryn ; Spangenberg, German ; Rochfort, Simone ; Quinn, Jane. / A functional metabolomics analysis of lolitrem B and its biosynthetic intermediates in the murine brain. Abstract from 10th International Symposium on Poisonous Plants , St George , United States.1 p.
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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. Lolitrem B is the endpoint in a biosynthetic pathway of indole diterpenoid toxins present in fodder yet the neuroactive status of it’s pathways intermediates remains undefined. To define the effects of lolitrem B and it’s pathway intermediates terpendoles B, C and E in the brain, a functional metabolomic study was undertaken in which cordination and tremor were quantified and metabolomic profiling undertaken to determine quantification anad relative abundance of both toxin and key neurotransmitters in various brain regions. Marked differences were observed in the duration of tremor and coordination between pathway members, with some showing protracted effects and others none at all. Quantification of lolitrem B using LCMS/MS QQQ identified presence of Lolitrem B in liver and kidney, cerebral cortex, thalamus and brain stem but not in cerebellum. Metabolomic profiling by LCMS/MS-QToF of brain isolated from intoxicated animals using showed significnat variation in targetted neurotransmitter and amino acid profiles over time. This study demonstrates for the first time bioaccumulation of lolitrem B in the brain, with absence of detectable levels of toxin in the cerebellum, as determining a dynamic catecholenergic response over time. This data is indicates that the indole diterpenoid toxins induce alterations in catecholamine pathways in the brain as well identifying pathway intermediates with non-tremorgenic profiles. This study idetnfies a functional metabolomic approach for physiological profiling of neurotoxic agents in the brain.",
keywords = "Perennial ryegrass, Perennial ryegrass toxicosis, metabolomics, LC-MS/MS, lolitrem B",
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Reddy, P, Combs, M, Read, E, Deseo, M, Jaehne, E, Van Den Buuse, M, Guthridge, K, Spangenberg, G, Rochfort, S & Quinn, J 2018, 'A functional metabolomics analysis of lolitrem B and its biosynthetic intermediates in the murine brain' 10th International Symposium on Poisonous Plants , St George , United States, 16/09/18 - 20/09/18, pp. 18.

A functional metabolomics analysis of lolitrem B and its biosynthetic intermediates in the murine brain. / Reddy, Priyanka; Combs, Martin; Read, Elizabeth; Deseo, Myrna; Jaehne, Emily; Van Den Buuse, Maarten; Guthridge, Kathryn ; Spangenberg, German; Rochfort, Simone; Quinn, Jane.

2018. 18 Abstract from 10th International Symposium on Poisonous Plants , St George , United States.

Research output: Other contribution to conferenceAbstract

TY - CONF

T1 - A functional metabolomics analysis of lolitrem B and its biosynthetic intermediates in the murine brain

AU - Reddy, Priyanka

AU - Combs, Martin

AU - Read, Elizabeth

AU - Deseo, Myrna

AU - Jaehne, Emily

AU - Van Den Buuse, Maarten

AU - Guthridge, Kathryn

AU - Spangenberg, German

AU - Rochfort, Simone

AU - Quinn, Jane

PY - 2018

Y1 - 2018

N2 - 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. Lolitrem B is the endpoint in a biosynthetic pathway of indole diterpenoid toxins present in fodder yet the neuroactive status of it’s pathways intermediates remains undefined. To define the effects of lolitrem B and it’s pathway intermediates terpendoles B, C and E in the brain, a functional metabolomic study was undertaken in which cordination and tremor were quantified and metabolomic profiling undertaken to determine quantification anad relative abundance of both toxin and key neurotransmitters in various brain regions. Marked differences were observed in the duration of tremor and coordination between pathway members, with some showing protracted effects and others none at all. Quantification of lolitrem B using LCMS/MS QQQ identified presence of Lolitrem B in liver and kidney, cerebral cortex, thalamus and brain stem but not in cerebellum. Metabolomic profiling by LCMS/MS-QToF of brain isolated from intoxicated animals using showed significnat variation in targetted neurotransmitter and amino acid profiles over time. This study demonstrates for the first time bioaccumulation of lolitrem B in the brain, with absence of detectable levels of toxin in the cerebellum, as determining a dynamic catecholenergic response over time. This data is indicates that the indole diterpenoid toxins induce alterations in catecholamine pathways in the brain as well identifying pathway intermediates with non-tremorgenic profiles. This study idetnfies a functional metabolomic approach for physiological profiling of neurotoxic agents in the brain.

AB - 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. Lolitrem B is the endpoint in a biosynthetic pathway of indole diterpenoid toxins present in fodder yet the neuroactive status of it’s pathways intermediates remains undefined. To define the effects of lolitrem B and it’s pathway intermediates terpendoles B, C and E in the brain, a functional metabolomic study was undertaken in which cordination and tremor were quantified and metabolomic profiling undertaken to determine quantification anad relative abundance of both toxin and key neurotransmitters in various brain regions. Marked differences were observed in the duration of tremor and coordination between pathway members, with some showing protracted effects and others none at all. Quantification of lolitrem B using LCMS/MS QQQ identified presence of Lolitrem B in liver and kidney, cerebral cortex, thalamus and brain stem but not in cerebellum. Metabolomic profiling by LCMS/MS-QToF of brain isolated from intoxicated animals using showed significnat variation in targetted neurotransmitter and amino acid profiles over time. This study demonstrates for the first time bioaccumulation of lolitrem B in the brain, with absence of detectable levels of toxin in the cerebellum, as determining a dynamic catecholenergic response over time. This data is indicates that the indole diterpenoid toxins induce alterations in catecholamine pathways in the brain as well identifying pathway intermediates with non-tremorgenic profiles. This study idetnfies a functional metabolomic approach for physiological profiling of neurotoxic agents in the brain.

KW - Perennial ryegrass

KW - Perennial ryegrass toxicosis

KW - metabolomics

KW - LC-MS/MS

KW - lolitrem B

M3 - Abstract

SP - 18

ER -

Reddy P, Combs M, Read E, Deseo M, Jaehne E, Van Den Buuse M et al. A functional metabolomics analysis of lolitrem B and its biosynthetic intermediates in the murine brain. 2018. Abstract from 10th International Symposium on Poisonous Plants , St George , United States.