Novel insights into mitochondrial molecular targets of iron-induced neurodegeneration: Reversal by cannabidiol

作者：da Silva Vanessa Kappel; de Freitas Betania Souza; Dornelles Victoria Campos; Kist Luiza Wilges; Bogo Mauricio Reis; Silva Milena Carvalho; Streck Emilio Luiz; Hallak Jaime Eduardo; Zuardi Antonio Waldo; Crippa Jose Alexandre S; Schroder Nadja^*

来源：Brain Research Bulletin, 2018, 139: 1-8.

DOI：10.1016/j.brainresbull.2018.01.014

• Cannabidiol
• Neurodegeneration
• Mitochondria
• mtDNA methylation
• Iron
• Mitochondrial ferritin

Evidence has demonstrated iron accumulation in specific brain regions of patients suffering from neurodegenerative disorders, and this metal has been recognized as a contributing factor for neurodegeneration. Using an experimental model of brain iron accumulation, we have shown that iron induces severe memory deficits that are accompanied by oxidative stress, increased apoptotic markers, and decreased synaptophysin in the hippo campus of rats. The present study aims to characterize iron loading effects as well as to determine the molecular targets of cannabidiol (CBD), the main non-psychomimetic compound of Cannabis saliva, on mitochondria. Rats received iron in the neonatal period and CBD for 14 days in adulthood. Iron induced mitochondrial DNA (mtDNA) deletions, decreased epigenetic modulation of mtDNA, mitochondrial ferritin levels, and succinate dehydrogenase activity. CBD rescued mitochondria] ferritin and epigenetic modulation of mtDNA, and restored succinate dehydrogenase activity in iron-treated rats. These findings provide new insights into molecular targets of iron neurotoxicity and give support for the use of CBD as a disease modifying agent in the treatment of neurodegenerative diseases.

• 出版日期2018-5