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Insulin and SB-216763, a GSK3β inhibitor, reduce methamphetamine toxicity in human neuroblastoma and rat primary midbrain cells

Year: 2025

Type: article

Abstract: Introduction: Methamphetamine (MA) induces cell death through several mechanisms.Insulin has an important role in cell proliferation and apoptosis via GSK3β inactivation.Here, we evaluated the effect of insulin and SB-216763, a selective GSK3β inhibitor, on MA-induced cell death in neuroblastoma SH-SY5Y, and rat primary midbrain cells.Methods: Human SH-SY5Y and rat primary midbrain cells extracted from E14.5 rat embryo were treated with insulin (0.005-0.15U) or SB-216763 (0.5-9µM) with or without MA (5mM).The cell viabil-ity was assessed after 24, 48, and 72 h.TNFα, Bax, Bim, and Bcl2 genes expression were exam-ined in primary midbrain cells after 72 h of treatment with 5mM MA, insulin (0.05U), and SB-216763 (3µM).Results: MA significantly decreased the viability of human SH-SY5Y and rat primary midbrain cells, and insulin and SB-216763 could increase it.In addition, elevated expression of TNFα and Bax fol-lowing MA was attenuated by insulin and SB-216763 in primary midbrain cells.Conclusion: These findings demonstrated that MA decreases the cell viability of rat primary midbrain cells, at least in part, by upregulation of inflammatory and apoptotic factors, and treatment with insulin and SB-216763 could attenuate MA toxicity. www.phypha.ir/ppj Experimental Research ArticlePhysiology and Pharmacology 29 (2025) 323-334 Methamphetamine (MA) can induce long-term deficits in monoaminergic, especially dopaminergic, systems.Reduction in dopaminergic neuron markers and degeneration of neuronal and glial cells in various brain regions have been shown in animal models and humans following MA administration (Ares-Santos et al., 2014;Ferrucci et al., 2022;Kousik et al., 2014).MA-induced neurotoxic effects are mediated through several neurotoxic mechanisms like, neuroinflammation, excitotoxicity, mitochondrial dysfunction, and oxidative stress (Marshall and O'Dell 2012).Several in-vitro studies Physiology and Pharmacology 29 (2025) 323-334 | 324 Insulin and GSK3β inhibitor effects on methamphetamine-induced toxicity

Source: Economy of Tajikistan

DOI: 10.61882/phypha.29.3.323

Authors: Neda Valian, Leila Dargahi, Mansooreh Heravi, Abolhassan Ahmadiani

Institutions: Shahid Beheshti University, Shahid Beheshti University of Medical Sciences, Pasteur Institute of Iran

Language: English

Topic: Wnt/β-catenin signaling in development and cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funder: Shahid Beheshti University of Medical Sciences