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Human Astrocyte Spheroids as Suitable In Vitro Screening Model to Evaluate Synthetic Cannabinoid MAM2201-Induced Effects on CNS

There is growing concern about the consumption of synthetic cannabinoids (SCs), one of the largest groups of new psychoactive substances, its consequence on human health (general population and workers), and the continuous placing of new SCs on the market. Although drug-induced alterations in neuron...

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Autores principales: De Simone, Uliana, Pignatti, Patrizia, Villani, Laura, Russo, Luciana Alessandra, Sargenti, Azzurra, Bonetti, Simone, Buscaglia, Eleonora, Coccini, Teresa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9861655/
https://www.ncbi.nlm.nih.gov/pubmed/36674936
http://dx.doi.org/10.3390/ijms24021421
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author De Simone, Uliana
Pignatti, Patrizia
Villani, Laura
Russo, Luciana Alessandra
Sargenti, Azzurra
Bonetti, Simone
Buscaglia, Eleonora
Coccini, Teresa
author_facet De Simone, Uliana
Pignatti, Patrizia
Villani, Laura
Russo, Luciana Alessandra
Sargenti, Azzurra
Bonetti, Simone
Buscaglia, Eleonora
Coccini, Teresa
author_sort De Simone, Uliana
collection PubMed
description There is growing concern about the consumption of synthetic cannabinoids (SCs), one of the largest groups of new psychoactive substances, its consequence on human health (general population and workers), and the continuous placing of new SCs on the market. Although drug-induced alterations in neuronal function remain an essential component for theories of drug addiction, accumulating evidence indicates the important role of activated astrocytes, whose essential and pleiotropic role in brain physiology and pathology is well recognized. The study aims to clarify the mechanisms of neurotoxicity induced by one of the most potent SCs, named MAM-2201 (a naphthoyl-indole derivative), by applying a novel three-dimensional (3D) cell culture model, mimicking the physiological and biochemical properties of brain tissues better than traditional two-dimensional in vitro systems. Specifically, human astrocyte spheroids, generated from the D384 astrocyte cell line, were treated with different MAM-2201 concentrations (1–30 µM) and exposure times (24–48 h). MAM-2201 affected, in a concentration- and time-dependent manner, the cell growth and viability, size and morphological structure, E-cadherin and extracellular matrix, CB1-receptors, glial fibrillary acidic protein, and caspase-3/7 activity. The findings demonstrate MAM-2201-induced cytotoxicity to astrocyte spheroids, and support the use of this human 3D cell-based model as species-specific in vitro tool suitable for the evaluation of neurotoxicity induced by other SCs.
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spelling pubmed-98616552023-01-22 Human Astrocyte Spheroids as Suitable In Vitro Screening Model to Evaluate Synthetic Cannabinoid MAM2201-Induced Effects on CNS De Simone, Uliana Pignatti, Patrizia Villani, Laura Russo, Luciana Alessandra Sargenti, Azzurra Bonetti, Simone Buscaglia, Eleonora Coccini, Teresa Int J Mol Sci Article There is growing concern about the consumption of synthetic cannabinoids (SCs), one of the largest groups of new psychoactive substances, its consequence on human health (general population and workers), and the continuous placing of new SCs on the market. Although drug-induced alterations in neuronal function remain an essential component for theories of drug addiction, accumulating evidence indicates the important role of activated astrocytes, whose essential and pleiotropic role in brain physiology and pathology is well recognized. The study aims to clarify the mechanisms of neurotoxicity induced by one of the most potent SCs, named MAM-2201 (a naphthoyl-indole derivative), by applying a novel three-dimensional (3D) cell culture model, mimicking the physiological and biochemical properties of brain tissues better than traditional two-dimensional in vitro systems. Specifically, human astrocyte spheroids, generated from the D384 astrocyte cell line, were treated with different MAM-2201 concentrations (1–30 µM) and exposure times (24–48 h). MAM-2201 affected, in a concentration- and time-dependent manner, the cell growth and viability, size and morphological structure, E-cadherin and extracellular matrix, CB1-receptors, glial fibrillary acidic protein, and caspase-3/7 activity. The findings demonstrate MAM-2201-induced cytotoxicity to astrocyte spheroids, and support the use of this human 3D cell-based model as species-specific in vitro tool suitable for the evaluation of neurotoxicity induced by other SCs. MDPI 2023-01-11 /pmc/articles/PMC9861655/ /pubmed/36674936 http://dx.doi.org/10.3390/ijms24021421 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
De Simone, Uliana
Pignatti, Patrizia
Villani, Laura
Russo, Luciana Alessandra
Sargenti, Azzurra
Bonetti, Simone
Buscaglia, Eleonora
Coccini, Teresa
Human Astrocyte Spheroids as Suitable In Vitro Screening Model to Evaluate Synthetic Cannabinoid MAM2201-Induced Effects on CNS
title Human Astrocyte Spheroids as Suitable In Vitro Screening Model to Evaluate Synthetic Cannabinoid MAM2201-Induced Effects on CNS
title_full Human Astrocyte Spheroids as Suitable In Vitro Screening Model to Evaluate Synthetic Cannabinoid MAM2201-Induced Effects on CNS
title_fullStr Human Astrocyte Spheroids as Suitable In Vitro Screening Model to Evaluate Synthetic Cannabinoid MAM2201-Induced Effects on CNS
title_full_unstemmed Human Astrocyte Spheroids as Suitable In Vitro Screening Model to Evaluate Synthetic Cannabinoid MAM2201-Induced Effects on CNS
title_short Human Astrocyte Spheroids as Suitable In Vitro Screening Model to Evaluate Synthetic Cannabinoid MAM2201-Induced Effects on CNS
title_sort human astrocyte spheroids as suitable in vitro screening model to evaluate synthetic cannabinoid mam2201-induced effects on cns
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9861655/
https://www.ncbi.nlm.nih.gov/pubmed/36674936
http://dx.doi.org/10.3390/ijms24021421
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