MAM-2201, One of the Most Potent-Naphthoyl Indole Derivative-Synthetic Cannabinoids, Exerts Toxic Effects on Human Cell-Based Models of Neurons and Astrocytes.
Human D384 astrocytes
Human SH-SY5H neurons
Human neuron-like cells
Neurotoxicity
Novel psychoactive substances
Preclinical studies
Journal
Neurotoxicity research
ISSN: 1476-3524
Titre abrégé: Neurotox Res
Pays: United States
ID NLM: 100929017
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
received:
29
10
2020
accepted:
25
04
2021
revised:
26
03
2021
pubmed:
5
5
2021
medline:
18
12
2021
entrez:
4
5
2021
Statut:
ppublish
Résumé
Considering the consequences on human health, in general population and workplace, associated with the use of new psychoactive substances and their continuous placing on the market, novel in vitro models for neurotoxicology research, applying human-derived CNS cells, may provide a means to understand the mechanistic basis of molecular and cellular alterations in brain. Cytotoxic effects of MAM-2201, a potent-naphthoyl indole derivative-synthetic cannabinoid, have been evaluated applying a panel of human cell-based models of neurons and astrocytes, testing different concentrations (1-30 µM) and exposure times (3-24-48 h). MAM-2201 induced toxicity in primary neuron-like cells (hNLCs), obtained from transdifferentiation of mesenchymal stem cells derived from human umbilical cord. Effects occurred in a concentration- and time-dependent manner. The lowest concentration affecting cell viability, metabolic function, apoptosis, morphology, and neuronal markers (MAP-2, NSE) was 5 μM, and even 1 μM induced apoptosis. Effects appeared early (3 h) and persisted after 24 and 48 h. Similar behavior was evidenced for human D384-astrocytes treated with MAM-2201. Differently, human SH-SY5Y-neurons, both differentiated and undifferentiated, were not sensitive to MAM-2201. On D384, the different altered endpoints were reversed, attenuated, or not antagonized by AM251 indicating that CB1 receptors may partially mediate MAM-2201-induced cytotoxicity. While in hNLCs, all toxic effects caused by MAM-2201 were apparently unrelated to CB-receptors since they were not evidenced by immunofluorescence. The present in vitro findings demonstrate the cytotoxicity of MAM-2201 on human primary neurons (hNLCs) and astrocytes cell line (D384), and support the use of these cellular models as species-specific in vitro tools suitable to clarify the neurotoxicity mechanisms of synthetic cannabinoids.
Identifiants
pubmed: 33945101
doi: 10.1007/s12640-021-00369-3
pii: 10.1007/s12640-021-00369-3
doi:
Substances chimiques
1-(5-fluoropentyl)-3-(4-methyl-1-naphthoyl)indole
0
Cannabinoids
0
Indoles
0
Naphthalenes
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1251-1273Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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