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

Autor: Reddy P; Agriculture Victoria, AgriBio, Centre for AgriBioscience, Bundoora, Victoria, 3083, Australia. priyanka.reddy@agriculture.vic.gov.au., Vincent D; Agriculture Victoria, AgriBio, Centre for AgriBioscience, Bundoora, Victoria, 3083, Australia., Hemsworth J; Agriculture Victoria, AgriBio, Centre for AgriBioscience, Bundoora, Victoria, 3083, Australia., Ezernieks V; Agriculture Victoria, AgriBio, Centre for AgriBioscience, Bundoora, Victoria, 3083, Australia., Guthridge K; Agriculture Victoria, AgriBio, Centre for AgriBioscience, Bundoora, Victoria, 3083, Australia., Spangenberg GC; Agriculture Victoria, AgriBio, Centre for AgriBioscience, Bundoora, Victoria, 3083, Australia.; School of Applied Systems Biology, La Trobe University, Bundoora, Victoria, 3083, Australia., Rochfort SJ; Agriculture Victoria, AgriBio, Centre for AgriBioscience, Bundoora, Victoria, 3083, Australia.; School of Applied Systems Biology, La Trobe University, Bundoora, Victoria, 3083, Australia.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Oct 01; Vol. 11 (1), pp. 19542. Date of Electronic Publication: 2021 Oct 01.
DOI: 10.1038/s41598-021-98870-4
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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