Glial Cell Response to 3,4-(±)-Methylenedioxymethamphetamine and Its Metabolites
| العنوان: | Glial Cell Response to 3,4-(±)-Methylenedioxymethamphetamine and Its Metabolites |
|---|---|
| المؤلفون: | Serrine S. Lau, Terrence J. Monks, Joseph M. Herndon, Aram B. Cholanians |
| المصدر: | Toxicological Sciences. 138:130-138 |
| بيانات النشر: | Oxford University Press (OUP), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, N-Methyl-3,4-methylenedioxyamphetamine, Sulfides, Pharmacology, Toxicology, Serotonergic, Hippocampus, Rats, Sprague-Dawley, In vivo, Glial Fibrillary Acidic Protein, mental disorders, medicine, Animals, 3,4-Methylenedioxyamphetamine, Cells, Cultured, Cell Proliferation, Injections, Intraventricular, Neurons, Dose-Response Relationship, Drug, Glial fibrillary acidic protein, biology, Microglia, Chemistry, Neurotoxicity, MDMA, medicine.disease, Immunohistochemistry, Coculture Techniques, Rats, medicine.anatomical_structure, Astrocytes, biology.protein, Neuroglia, Neurotoxicity Syndromes, psychological phenomena and processes, Ex vivo, Research Article, medicine.drug |
| الوصف: | 3,4-(±)-Methylenedioxymethamphetamine (MDMA) and 3,4-(±)-methylenedioxyamphetamine (MDA), a primary metabolite of MDMA, are phenylethylamine derivatives that cause serotonergic neurotoxicity. Although several phenylethylamine derivatives activate microglia, little is known about the effects of MDMA on glial cells, and evidence of MDMA-induced microglial activation remains ambiguous. We initially determined microglial occupancy status of the parietal cortex in rats at various time points following a single neurotoxic dose of MDMA (20mg/kg, SC). A biphasic microglial response to MDMA was observed, with peak microglial occupancy occurring 12- and 72-h post-MDMA administration. Because direct injection of MDMA into the brain does not produce neurotoxicity, the glial response to MDMA metabolites was subsequently examined in vivo and in vitro. Rats were treated with MDA (20mg/kg, SC) followed by ex vivo biopsy culture to determine the activation of quiescent microglia. A reactive microglial response was observed 72 h after MDA administration that subsided by 7 days. In contrast, intracerebroventricular (ICV) administration of MDA failed to produce a microglial response. However, thioether metabolites of MDA derived from α-methyldopamine (α-MeDA) elicited a robust microglial response following icv injection. We subsequently determined the direct effects of various MDMA metabolites on primary cultures of E18 hippocampal mixed glial and neuronal cells. 5-(Glutathion-S-yl)-α-MeDA, 2,5-bis-(glutathion-S-yl)-α-MeDA, and 5-(N-acetylcystein-S-yl)-α-MeDA all stimulated the proliferation of glial fibrillary acidic protein-positive astrocytes at a dose of 10 µM. The findings indicate that glial cells are activated in response to MDMA/MDA and support a role for thioether metabolites of α-MeDA in the neurotoxicity. |
| تدمد: | 1096-0929 1096-6080 |
| DOI: | 10.1093/toxsci/kft275 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::96d87f7a50b7615fc756db9becbd7bff https://doi.org/10.1093/toxsci/kft275 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....96d87f7a50b7615fc756db9becbd7bff |
| قاعدة البيانات: | OpenAIRE |
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