Pathophysiological impacts of 5-MeO-MiPT on zebrafish (Danio rerio) via the Gαq/11-PLCβ signaling pathway
Sen Zhao, Meng Liu, Jinyuan Chen, Liang Meng, Yanjiao Wang
Ecotoxicology and Environmental Safety August 30, 2024 Peer reviewed DOI: 10.1016/j.ecoenv.2024.116969 via OpenAlex
Summary
5-MeO-MiPT, a novel psychoactive substance derived from tryptamines, was injected into zebrafish for 30 days, leading to behavioral inhibition and oxidative stress. The study identified significant changes in the expression of 13 genes, such as ucp1 and grik3, mediated by specific signaling pathways. These findings provide insights into the toxicological effects of 5-MeO-MiPT and suggest mechanisms that may inhibit normal behavior in zebrafish, paving the way for future research on tryptamine-based substances.
Study at a glance
| Population | zebrafish |
|---|---|
| Key finding | 5-MeO-MiPT substantially influences the transcription and expression of 13 selected genes in zebrafish, mediated by the Gα q/11 -PLC β signaling pathway. |
Abstract
Novel Psychoactive Substances (NPS) derived from tryptamines has been detected in aquatic environments, leading to environmental toxicology concerns. However, the specific toxicological mechanism, underlying these NPS, remains unclear. In our previous work, we used 5-Methoxy-N-isopropyl-N-methyltryptamine (5-MeO-MiPT) as the representative drug for NPS, and found that, 5-MeO-MiPT led to obvious behavioral inhibition and oxidative stress responses in zebrafishes model. In this study, Zebrafish were injected with varying concentrations of 5-MeO-MiPT for 30 days. RNA-seq, qPCR, metabolomics, and histopathological analyses were conducted to assess gene expression and tissue integrity. This study confirms that 5-MeO-MiPT substantially influences the transcription and expression of 13 selected genes, including ucp1 , pet100 , grik3 , and grik4 , mediated by the Gα q/11 -PLC β signaling pathway. We elucidate the molecular mechanism that 5-MeO-MiPT can inhibit DAG-Ca 2+ /Pkc/Erk, Pkc/Pla2/PLCs and Ca 2+ /Camk Ⅱ/NMDA, while enhance Ca 2+ /Creb. Those secondary signaling pathways may be the mechanisms mediating 5-MeO-MiPT inhibiting normal behavior in zebrafish. These findings offer novel insights into the toxicological effects and addiction mechanisms of 5-MeO-MiPT. Moreover, it presents promising avenues for investigating other tryptamine-based NPS and offers a new direction for diagnosing and treating liver-brain pathway-related diseases. • The study investigated 5-MeO-MiPT's impact on zebrafish. • It caused oxidative stress and behavioral inhibition. • RNA-seq and qPCR analyses revealed gene expression changes. • Gα q/11 -PLC β signaling mediated these effects.