Neurotoxic effects of hallucinogenic drugs 25H-NBOMe and 25H-NBOH in organotypic hippocampal cultures

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dc.creatorLarissa Marcely Gomes Cassiano
dc.creatorMarina da Silva Oliveira
dc.creatorWellington Alves de Barros
dc.creatorÂngelo de Fátima
dc.creatorRoney Santos Coimbra
dc.date.accessioned2024-11-06T22:48:28Z
dc.date.accessioned2025-09-09T00:02:04Z
dc.date.available2024-11-06T22:48:28Z
dc.date.issued2023
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.description.sponsorshipOutra Agência
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.1016/j.heliyon.2023.e17720
dc.identifier.issn2405-8440
dc.identifier.urihttps://hdl.handle.net/1843/77855
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofHeliyon
dc.rightsAcesso Aberto
dc.subjectFenetilamina
dc.subjectNeurotoxicologia
dc.subjectNeurologia do desenvolvimento
dc.subject.other25H-NBOMe
dc.subject.other25H-NBOH
dc.subject.otherPhenethylamines
dc.subject.otherOrganotypic hippocampal culture
dc.subject.otherNeurotoxicity
dc.subject.otherNeurogenesis
dc.titleNeurotoxic effects of hallucinogenic drugs 25H-NBOMe and 25H-NBOH in organotypic hippocampal cultures
dc.typeArtigo de periódico
local.citation.issue7
local.citation.spagee17720
local.citation.volume9
local.description.resumoIntroduction: NBOMes and NBOHs are psychoactive drugs derived from phenethylamines and have hallucinogenic effects due to their strong agonism to serotonin 5-HT2A receptors. Although cases of toxicity associated with the recreational use of substituted phenethylamines are frequently reported, there is a lack of information on the possible neurotoxic effects of NBOMe and NBOH in the brain hippocampus, a major neurogenesis region. Objectives: Introduction NBOMes and NBOHs are psychoactive drugs derived from phenethylamines and have hallucinogenic effects due to their strong agonism to serotonin 5-HT2A receptors. Although cases of toxicity associated with the recreational use of substituted phenethylamines are frequently reported, there is a lack of information on the possible neurotoxic effects of NBOMe and NBOH in the brain hippocampus, a major neurogenesis region. Objectives This study aimed at assessing the phenotypic and molecular effects of prolonged exposure of the hippocampus to the drugs 25H-NBOMe and 25H-NBOH. Methods The ex vivo organotypic culture model of hippocampal slices (OHC) was used to investigate, by immunofluorescence and confocal microscopy, and transcriptome analyses, the mechanisms associated with the neurotoxicity of 25H-NBOMe and 25H-NBOH. Results Reduction in the density of mature neurons in the OHCs occurred after two and seven days of exposure to 25H-NBOMe and 25H-NBOH, respectively. After the withdrawal of 25H-NBOMe, the density of mature neurons in the OHCs stabilized. In contrast, up to seven days after 25H-NBOH removal from the culture medium, progressive neuron loss was still observed in the OHCs. Interestingly, the exposure to 25H-NBOH induced progenitor cell differentiation, increasing the density of post-mitotic neurons in the OHCs. Corroborating these findings, the functional enrichment analysis of differentially expressed genes in the OHCs exposed to 25H-NBOH revealed the activation of WNT/Beta-catenin pathway components associated with neurogenesis. During and after the exposure to 25H-NBOMe or 25H-NBOH, gene expression patterns related to the activation of synaptic transmission and excitability of neurons were identified. Furthermore, activation of signaling pathways and biological processes related to addiction and oxidative stress and inhibition of the inflammatory response were observed after the period of drug exposure. Conclusion: 25H-NBOMe and 25H-NBOH disrupt the balance between neurogenesis and neuronal death in the hippocampus and, although chemically similar, have distinct neurotoxicity mechanisms. This study aimed at assessing the phenotypic and molecular effects of prolonged exposure of the hippocampus to the drugs 25H-NBOMe and 25H-NBOH. Methods: The ex vivo organotypic culture model of hippocampal slices (OHC) was used to investigate, by immunofluorescence and confocal microscopy, and transcriptome analyses, the mechanisms associated with the neurotoxicity of 25H-NBOMe and 25H-NBOH. Results: Reduction in the density of mature neurons in the OHCs occurred after two and seven days of exposure to 25H-NBOMe and 25H-NBOH, respectively. After the withdrawal of 25H-NBOMe, the density of mature neurons in the OHCs stabilized. In contrast, up to seven days after 25H-NBOH removal from the culture medium, progressive neuron loss was still observed in the OHCs. Interestingly, the exposure to 25H-NBOH induced progenitor cell differentiation, increasing the density of post-mitotic neurons in the OHCs. Corroborating these findings, the functional enrichment analysis of differentially expressed genes in the OHCs exposed to 25H-NBOH revealed the activation of WNT/Beta-catenin pathway components associated with neurogenesis. During and after the exposure to 25H-NBOMe or 25H-NBOH, gene expression patterns related to the activation of synaptic transmission and excitability of neurons were identified. Furthermore, activation of signaling pathways and biological processes related to addiction and oxidative stress and inhibition of the inflammatory response were observed after the period of drug exposure. Conclusion: 25H-NBOMe and 25H-NBOH disrupt the balance between neurogenesis and neuronal death in the hippocampus and, although chemically similar, have distinct neurotoxicity mechanisms.
local.identifier.orcidhttps://orcid.org/0000-0002-6941-0863
local.identifier.orcidhttps://orcid.org/0000-0002-6332-5254
local.identifier.orcidhttps://orcid.org/0000-0002-3479-0720
local.identifier.orcidhttps://orcid.org/0000-0003-2344-5590
local.identifier.orcidhttps://orcid.org/0000-0002-9204-0573
local.publisher.countryBrasil
local.publisher.departmentICX - DEPARTAMENTO DE QUÍMICA
local.publisher.initialsUFMG
local.url.externahttps://www.sciencedirect.com/science/article/pii/S2405844023049289

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