Neuronal Mitochondrial Trafficking Impairment: The Cause or a Consequence of Neuronal Dysfunction Caused by Amphetamine-Like Drugs
Author(s): Daniel Josôe Barbosa, Rom`an Serrat, Luôñsa Maria Ferreira, Paula Sôerio Branco, Maria de Lourdes Bastos, JoÃÂao Paulo Capela, Eduardo Soriano, and Fôelix Carvalho
Abstract
Drugs of abuse cause a variety of complex neuronal events at the cellular level, including changes in membrane excitability and neurotransmission, activation of complex signaling pathways, altered synaptic physiology and structural changes, and drug-evoked synaptic plasticity and neurotoxicity, which mediate both acuteand long-lasting effects and addiction. Neuronal mitochondria are highly dynamic organelles that, by undergoing fusion and fission events, are efficiently translocated along the neuronal processes, frequently changing direction, pausing or switching to persistent docking. The neuronal integrity and functionality are dependent upon the proper maintenance of a healthy mitochondrial population and their efficient distribution. There is a general consensus that mitochondrial-dependent pathways can provide a major understanding concerning pathological processes underlying neurotoxicity of drugs of abuse. As such, it is plausible to consider that alterations on mitochondrial trafficking may be key players on the neuronal effects mediated by these drugs. This work aims to provide a comprehensive and up-to-date review of the data linking mitochondrial trafficking impairment to amphetamine-like drugs, and, thus, contribute to a better understanding of their neuronal effects. Additionally, new research data describing alterations in neuronal mitochondrial trafficking for 3,4-methylenedioxymethamphetamine (MDMA; “ecstasy”) conjugated metabolites 5-(glutathion-S-yl)-N-methyl-α-methyldopamine [5-(GSH)-N-Me-α-MeDA] and 5-(N-acetylcystein-S-yl)-N-methyl-α- methyldopamine [5-(NAC)-N-Me-α-MeDA] are also provided.
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