Brain-derived neurotrophic factor protects serotonergic neurons against 3,4-methylenedioxymethamphetamine (“Ecstasy”) induced cytoskeletal damage
Francesco Bavato, Serena Stamatakos, C. M. Yde Ohki, Erich Seifritz, Patrizia Romualdi, E. Grünblatt, Boris B. Quednow
Journal of Neural Transmission June 1, 2022 DOI: 10.1007/s00702-022-02502-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | Rat raphe nucleus-derived serotonergic neuronal cell line (RN46A) |
| Interventions | MDMA BDNF |
| Measures | MTT, immunocytochemistry assay |
| Topics | MDMA Serotonin |
| Key findings | MDMA reduced cell viability and intracellular NfL levels in rat serotonergic RN46A cells, and BDNF co-treatment partially rescued these reductions. The authors argue that BDNF levels influence MDMA-induced serotonergic damage and propose BDNF as a target for neuroprotective interventions, while suggesting NfL may be useful for in vivo monitoring of drug-induced neurotoxicity. |
Abstract
Abstract3,4-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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 3
- White matter alterations in chronic MDMA use: Evidence from diffusion tensor imaging and neurofilament light chain blood levels NeuroImage: Clinical September 19, 2022
- Psychedelics in Multiple Sclerosis: Mechanisms, Challenges, and Prospects for Neuroimmune Modulation and Repair. Cells November 26, 2025
- MDMA (3,4-methylenedioxy-methamphetamine) Drug Addiction Mechanisms in the Brain April 8, 2024
Cites 16
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- MDMA enhances emotional empathy and prosocial behavior Social Cognitive and Affective Neuroscience October 4, 2013
- Reorganization of ascending 5-HT axon projections in animals previously exposed to the recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") Journal of Neuroscience August 1, 1995
- The Norepinephrine Transporter Inhibitor Reboxetine Reduces Stimulant Effects of MDMA (“Ecstasy”) in Humans Clinical Pharmacology & Therapeutics June 15, 2011
- Neuroanatomic specificity and time course of alterations in rat brain serotonergic pathways induced by MDMA (3,4‐methylenedioxymethamphetamine): Assessment using quantitative autoradiography Synapse August 1, 1991
and 11 more in the library