Neuroprotective effect of thyroid hormones on methamphetamine-induced neurotoxicity via cell surface receptors

Abstract

Thyroid hormones (THs) have an essential role in normal brain development and function. Methamphetamine (MA) is a widely abused psychostimulant that induces irreversible damages to neuronal cells. In the current study, we used rat primary hippocampal neurons (PHNs) to investigate the neuroprotective effect of THs against MA neurotoxicity. PHNs were prepared from 18-day rat embryos and cell viability was assessed using MTT assay, following treatment with various concentrations of MA, T3, T4 or tetrac, an integrin αvβ3 cell surface receptor antagonist. Our results showed that 7 mM MA induced an approximately 50 % reduction in the PHNs viability. Treatment with 800 nM T3 or 8 μM T4 protected PHNs against MA toxicity, an effect which was blocked in the presence of tetrac. These findings suggest that THs protect PHNs against MA-induced cell death by the activation of integrin αvβ3 cell surface receptors. So, targeting integrin αvβ3 receptors or using THs can be considered as promising therapeutic strategies to overcome MA neurotoxicity.