Journal article
MDMA-induced neurotoxicity of serotonin neurons involves autophagy and rilmenidine is protective against its pathobiology
LD Mercer, GC Higgins, CL Lau, AJ Lawrence, PM Beart
Neurochemistry International | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2017
Abstract
Toxicity of 3,4-methylenedioxymethamphetamine (MDMA) towards biogenic amine neurons is well documented and in primate brain predominantly affects serotonin (5-HT) neurons. MDMA induces damage of 5-HT axons and nerve fibres and intracytoplasmic inclusions. Whilst its pathobiology involves mitochondrially-mediated oxidative stress, we hypothesised MDMA possessed the capacity to activate autophagy, a proteostatic mechanism for degradation of cellular debris. We established a culture of ventral pons from embryonic murine brain enriched in 5-HT neurons to explore mechanisms of MDMA neurotoxicity and recruitment of autophagy, and evaluated possible neuroprotective actions of the clinically approve..
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Awarded by NHMRC
Funding Acknowledgements
The authors thank Servier (Paris) for generously providing rilmenidine. The advice of Dr Verena Wimmer is greatly appreciated. Supported in part by the NH&MRC Grant APP509217. PMB and AJL are supported by a NH&MRC Research Fellowships APP1020401 and APP1020737, respectively. The Morey Institute of Neuroscience and Mental Health receives infrastructure support from the Victorian State Government (Australia).