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- W2103602171 abstract "3,4-Methylenedioxymethamphetamine (MDMA; “ecstasy”) is a potentially neurotoxic recreational drug of abuse. Though the mechanisms involved are still not completely understood, formation of reactive metabolites and mitochondrial dysfunction contribute to MDMA-related neurotoxicity. Neuronal mitochondrial trafficking, and their targeting to synapses, is essential for proper neuronal function and survival, rendering neurons particularly vulnerable to mitochondrial dysfunction. Indeed, MDMA-associated disruption of Ca2+ homeostasis and ATP depletion have been described in neurons, thus suggesting possible MDMA interference on mitochondrial dynamics. In this study, we performed real-time functional experiments of mitochondrial trafficking to explore the role of in situ mitochondrial dysfunction in MDMA's neurotoxic actions. We show that the mixture of MDMA and six of its major in vivo metabolites, each compound at 10μM, impaired mitochondrial trafficking and increased the fragmentation of axonal mitochondria in cultured hippocampal neurons. Furthermore, the overexpression of mitofusin 2 (Mfn2) or dynamin-related protein 1 (Drp1) K38A constructs almost completely rescued the trafficking deficits caused by this mixture. Finally, in hippocampal neurons overexpressing a Mfn2 mutant, Mfn2 R94Q, with impaired fusion and transport properties, it was confirmed that a dysregulation of mitochondrial fission/fusion events greatly contributed to the reported trafficking phenotype. In conclusion, our study demonstrated, for the first time, that the mixture of MDMA and its metabolites, at concentrations relevant to the in vivo scenario, impaired mitochondrial trafficking and increased mitochondrial fragmentation in hippocampal neurons, thus providing a new insight in the context of “ecstasy”-induced neuronal injury." @default.
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- W2103602171 date "2014-03-04" @default.
- W2103602171 modified "2023-10-18" @default.
- W2103602171 title "The Mixture of “Ecstasy” and Its Metabolites Impairs Mitochondrial Fusion/Fission Equilibrium and Trafficking in Hippocampal Neurons, at In Vivo Relevant Concentrations" @default.
- W2103602171 cites W1531892057 @default.
- W2103602171 cites W1553062339 @default.
- W2103602171 cites W1576909217 @default.
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- W2103602171 cites W1960363048 @default.
- W2103602171 cites W1968135120 @default.
- W2103602171 cites W1969148884 @default.
- W2103602171 cites W1971191340 @default.
- W2103602171 cites W1974750801 @default.
- W2103602171 cites W1977966828 @default.
- W2103602171 cites W1981662243 @default.
- W2103602171 cites W1982988839 @default.
- W2103602171 cites W1983986186 @default.
- W2103602171 cites W1984280476 @default.
- W2103602171 cites W1985912952 @default.
- W2103602171 cites W1989130535 @default.
- W2103602171 cites W1989145123 @default.
- W2103602171 cites W1992085755 @default.
- W2103602171 cites W1993036354 @default.
- W2103602171 cites W1993696187 @default.
- W2103602171 cites W1996764498 @default.
- W2103602171 cites W2001929248 @default.
- W2103602171 cites W2010875415 @default.
- W2103602171 cites W2016532705 @default.
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- W2103602171 cites W2017509011 @default.
- W2103602171 cites W2020059513 @default.
- W2103602171 cites W2023283007 @default.
- W2103602171 cites W2030602441 @default.
- W2103602171 cites W2039409049 @default.
- W2103602171 cites W2044911918 @default.
- W2103602171 cites W2045085957 @default.
- W2103602171 cites W2047460306 @default.
- W2103602171 cites W2048841731 @default.
- W2103602171 cites W2049871369 @default.
- W2103602171 cites W2056704543 @default.
- W2103602171 cites W2057484845 @default.
- W2103602171 cites W2058117278 @default.
- W2103602171 cites W2058218592 @default.
- W2103602171 cites W2075421841 @default.
- W2103602171 cites W2084291672 @default.
- W2103602171 cites W2085883101 @default.
- W2103602171 cites W2094265661 @default.
- W2103602171 cites W2103607451 @default.
- W2103602171 cites W2106713530 @default.
- W2103602171 cites W2106877881 @default.
- W2103602171 cites W2120001424 @default.
- W2103602171 cites W2128951033 @default.
- W2103602171 cites W2132596838 @default.
- W2103602171 cites W2133377406 @default.
- W2103602171 cites W2135683358 @default.
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- W2103602171 cites W2151818435 @default.
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- W2103602171 doi "https://doi.org/10.1093/toxsci/kfu042" @default.
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