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Effects of ergotamine on the central nervous system using untargeted metabolomics analysis in a mouse model

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journal contribution
posted on 22.12.2021, 01:11 authored by Priyanka ReddyPriyanka Reddy, Delphine Vincent, Joanne Hemsworth, Vilnis Ezernieks, Kathryn Guthridge, German SpangenbergGerman Spangenberg, Simone RochfortSimone Rochfort
The ergot alkaloid ergotamine is produced by Claviceps purpurea, a parasitic fungus that commonly infects crops and pastures of high agricultural and economic importance. In humans and livestock, symptoms of ergotism include necrosis and gangrene, high blood pressure, heart rate, thermoregulatory dysfunction and hallucinations. However, ergotamine is also used in pharmaceutical applications to treat migraines and stop post-partum hemorrhage. To define its effects, metabolomic profiling of the brain was undertaken to determine pathways perturbed by ergotamine treatment. Metabolomic profiling identified the brainstem and cerebral cortex as regions with greatest variation. In the brainstem, dysregulation of the neurotransmitter epinephrine, and the psychoactive compound 2-arachidonylglycerol was identified. In the cerebral cortex, energy related metabolites isobutyryl-L-carnitine and S-3-oxodecanoyl cysteamine were affected and concentrations of adenylosuccinate, a metabolite associated with mental retardation, were higher. This study demonstrates, for the first time, key metabolomic pathways involved in the behavioural and physiological dysfunction of ergot alkaloid intoxicated animals.

Funding

The authors thank the Molecular Phenomics group at Agriculture Victoria and La Trobe University Central Animal House for their assistance. The research described here was funded by Agriculture Victoria, Dairy Australia through the Dairy Futures Cooperative Research Centre and DairyBio.

History

Publication Date

01/10/2021

Journal

Scientific Reports

Volume

11

Issue

1

Pagination

11p.

Publisher

Springer Nature

ISSN

2045-2322

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