Effects of olanzapine and haloperidol on mTORC1 signaling, dendritic outgrowth, and synaptic proteins in rat primary hippocampal neurons under toxic conditions

Neuroscience Letters
Sung Woo ParkJung Goo Lee

Abstract

Recent studies have demonstrated that antipsychotic drugs may activate mammalian target of rapamycin complex 1 (mTORC1) signaling in neurons. However, the relationship between mTORC1 signaling activation and currently prescribed antipsychotic drugs remains incompletely understood. The purpose of this study was to determine whether alterations in the level of mTORC1 signaling occur after rat primary hippocampal neurons are treated with olanzapine and haloperidol under toxic conditions. Additionally, we investigated whether these drugs affect dendritic outgrowth and synaptic protein expression through the mTORC1 signaling pathway. We measured changes in mTORC1-mediated and synaptic proteins by Western blotting assay under toxic conditions induced by B27 deprivation. Dendritic outgrowth was determined by a neurite assay. Olanzapine significantly increased the phosphorylated levels of mTORC1, its downstream effectors, and its upstream activators. The increased mTORC1 phosphorylation induced by olanzapine was significantly blocked by specific PI3K, MEK, or mTORC1 inhibitors. Olanzapine also increased dendritic outgrowth and synaptic proteins levels; all of these effects were blocked by rapamycin. However, haloperidol had none of the...Continue Reading

Citations

Mar 4, 2021·Biomedicines·Banny Silva Barbosa CorreiaLjubica Tasic

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