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Brain-derived neurotrophic factor protects serotonergic neurons against 3,4-methylenedioxymethamphetamine (“Ecstasy”) induced cytoskeletal damage
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 mark...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Vienna
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188522/ https://www.ncbi.nlm.nih.gov/pubmed/35420371 http://dx.doi.org/10.1007/s00702-022-02502-8 |
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author | Bavato, F. Stamatakos, S. Ohki, C. M. Yde Seifritz, E. Romualdi, P. Grünblatt, E. Quednow, B. B. |
author_facet | Bavato, F. Stamatakos, S. Ohki, C. M. Yde Seifritz, E. Romualdi, P. Grünblatt, E. Quednow, B. B. |
author_sort | Bavato, F. |
collection | PubMed |
description | 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00702-022-02502-8. |
format | Online Article Text |
id | pubmed-9188522 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Vienna |
record_format | MEDLINE/PubMed |
spelling | pubmed-91885222022-06-13 Brain-derived neurotrophic factor protects serotonergic neurons against 3,4-methylenedioxymethamphetamine (“Ecstasy”) induced cytoskeletal damage Bavato, F. Stamatakos, S. Ohki, C. M. Yde Seifritz, E. Romualdi, P. Grünblatt, E. Quednow, B. B. J Neural Transm (Vienna) Psychiatry and Preclinical Psychiatric Studies - Original Article 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00702-022-02502-8. Springer Vienna 2022-04-14 2022 /pmc/articles/PMC9188522/ /pubmed/35420371 http://dx.doi.org/10.1007/s00702-022-02502-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Psychiatry and Preclinical Psychiatric Studies - Original Article Bavato, F. Stamatakos, S. Ohki, C. M. Yde Seifritz, E. Romualdi, P. Grünblatt, E. Quednow, B. B. Brain-derived neurotrophic factor protects serotonergic neurons against 3,4-methylenedioxymethamphetamine (“Ecstasy”) induced cytoskeletal damage |
title | Brain-derived neurotrophic factor protects serotonergic neurons against 3,4-methylenedioxymethamphetamine (“Ecstasy”) induced cytoskeletal damage |
title_full | Brain-derived neurotrophic factor protects serotonergic neurons against 3,4-methylenedioxymethamphetamine (“Ecstasy”) induced cytoskeletal damage |
title_fullStr | Brain-derived neurotrophic factor protects serotonergic neurons against 3,4-methylenedioxymethamphetamine (“Ecstasy”) induced cytoskeletal damage |
title_full_unstemmed | Brain-derived neurotrophic factor protects serotonergic neurons against 3,4-methylenedioxymethamphetamine (“Ecstasy”) induced cytoskeletal damage |
title_short | Brain-derived neurotrophic factor protects serotonergic neurons against 3,4-methylenedioxymethamphetamine (“Ecstasy”) induced cytoskeletal damage |
title_sort | brain-derived neurotrophic factor protects serotonergic neurons against 3,4-methylenedioxymethamphetamine (“ecstasy”) induced cytoskeletal damage |
topic | Psychiatry and Preclinical Psychiatric Studies - Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188522/ https://www.ncbi.nlm.nih.gov/pubmed/35420371 http://dx.doi.org/10.1007/s00702-022-02502-8 |
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