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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University of Melbourne Researchers

Grants

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).