Search

3,4-methylenedioxymethamphetamine (MDMA) is a psychoactive substance used for recreational purposes. Possible clinical use of MDMA, in combination with psychotherapy, has been considered for the treatment of PTSD. However, MDMA causes neurotoxic effects and its use was associated with psychiatric symptoms, memory and cognitive deficits. To elucidate these aspects, the first aim of this study was to investigate the effects of acute and repeated MDMA treatment on BDNF/TrkB and HDACs in animal models. According to recent evidence about HDAC inhibitors, we used sodium butyrate to investigate its ability to affect MDMA-induced molecular and behavioral alterations. Moreover, considering that an alteration of BDNF has been reported in the brain of animals treated with psychoactive substances and in the blood of substance abusers, possible alterations of this neurotrophin levels were investigated in blood samples of MDMA users. Since different BDNF pools exist in plasma and serum, distinct determination of the neurotrophin were evaluated in both matrices. Furthermore, recent evidence has shown that neurofilaments can represent valid biomarkers of neural damage. Given the neurotoxic effects of ecstasy, we investigated neurofilaments in serotonergic neuronal cells. Particularly, we assessed MDMA effects on neurofilament proteins in differentiated serotonergic cells and we investigated if BDNF could protect serotonergic neurons from MDMA effects. Data showed that MDMA alters different crucial genes as well as the proteins involved in both substance use disorders and psychiatric conditions. Animal studies showed alterations both in BDNF pathways and in HDACs. Moreover, investigation in humans brought into view that peripheral BDNF could not reflect central BDNF and serum and plasma BDNF can express different types of this neurotrophin. Furthermore, data obtained in the differentiated serotonergic cell line highlight the useful role of NF-L as a biomarker of neuronal damage indu

Tobacco smoking remains without a doubt one of the leading causes of premature death worldwide. In combination with conventional protocols for smoking cessation, e-cigarettes have been proposed as a useful tool to quit smoking. Advertised as almost free of toxic effects, e-cigarettes have rapidly increased their popularity, becoming a sought-after device, especially among young people. Recently some health concerns about e-cigarette consumption are being raised. It is well known that they can release several toxic compounds, some of which are carcinogenic to humans, and emerging results are now outlining the risks related to the onset of respiratory and cardiovascular diseases and even cancer. The present review shows the emerging evidence about the role of technical components of the devices, the e-liquid composition as well as customization by consumers. The primary topics we discuss are the main toxicological aspects associated with e-cigarette consumption, focusing on the molecular pathways involved. Here it will be shown how exposure to e-cigarette aerosol induces stress/mitochondrial toxicity, DNA breaks/fragmentation following the same pathological pathways triggered by tobacco smoke, including the deregulation of molecular signalling axis associated with cancer progression and cell migration. Risk to fertility and pregnancy, as well as cardiovascular risk associated with e-cigarette use, have also been reported.

3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") use has been linked to persistent alterations of the brain serotonergic (5-HT) system in animal and human studies, but the molecular underpinnings are still unclear. Cytoskeletal structures such as neurofilament light chain (NfL) are promising markers of drug-induced brain toxicity and may be involved in MDMA neurotoxicity. The brain-derived neurotrophic factor (BDNF) promotes the growth and sprouting of 5-HT neurons and its differential response to MDMA administration was suggested to mediate dose- and region-dependent 5-HT damage by MDMA. However, the role of BDNF pre-treatment in preventing MDMA neurotoxicity and the potential effects of MDMA on NfL are still elusive. Therefore, a differentiated 5-HT neuronal cell line obtained from rat raphe nucleus (RN46A) was treated in vitro with either MDMA, BDNF, MDMA + BDNF, or vehicle. Cell viability (measured by MTT) and intracellular NfL levels (immunocytochemistry assay) were reduced by MDMA, but partially rescued by BDNF co-treatment. Our findings confirmed that BDNF levels can influence MDMA-induced 5-HT damage, and support BDNF to be a crucial target for neuroprotective interventions of the 5-HT system. We also provide evidence on the sensitivity of NfL to MDMA neurotoxicity, with potential implications for in-vivo monitoring of drug-induced neurotoxicity.