Agriculture Victoria, AgriBio, Centre for AgriBioscience, Bundoora, Victoria, 3083, Australia.
School of Applied Systems Biology, La Trobe University, Bundoora, Victoria, 3083, Australia.
Sci Rep. 2021 Oct 1;11(1):19542. doi: 10.1038/s41598-021-98870-4.
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.
麦角生物碱麦角胺是由麦角菌产生的，麦角菌是一种寄生真菌，通常感染具有高农业和经济重要性的作物和牧场。在人类和牲畜中，麦角中毒的症状包括坏死和坏疽、高血压、心率、体温调节功能障碍和幻觉。然而，麦角胺也用于药物应用中，以治疗偏头痛和阻止产后出血。为了确定其作用，对大脑进行了代谢组学分析，以确定受麦角胺治疗影响的途径。代谢组学分析确定了脑干和大脑皮层是变化最大的区域。在脑干中，发现了神经递质肾上腺素和精神活性化合物 2-花生四烯酰甘油的失调。在大脑皮层中，受影响的是与能量相关的代谢物异丁酰肉碱和 S-3-氧代癸酰半胱氨酸，并且与智力迟钝相关的代谢物腺苷酸琥珀酸的浓度更高。这项研究首次证明了参与麦角生物碱中毒动物行为和生理功能障碍的关键代谢途径。
