Transcriptomic and proteomic analyses of SH-SY5Y neuroblastoma cells treated with amisulpride.

Objective: Amisulpride, a substituted benzamide derivative, has a unique pharmacological profile characterised by a high affinity for dopaminergic D₂/D₃ receptors, as well as an affinity for 5-HT₇ receptors. Its effectiveness and safety surpass those of traditional antipsychotic drugs and multi-receptor antipsychotic medications in improving global symptoms, including both positive and negative symptoms. This makes it a compelling subject for study. However, the molecular mechanisms that contribute to its clinical efficacy in treating schizophrenia remain largely unexplored.

Methods: We assessed cell viability following amisulpride treatment using the MTT and a real-time cell viability assay. Subsequently, we conducted RNA-seq and LC-MS/MS analyses to identify differentially expressed genes and proteins in SH-SY5Y neuroblastoma cells treated with amisulpride.

Results: In the present study, we used RNA-seq analysis to identify downregulated expression of a transcriptional factor, FOSB, in amisulpride-treated SH-SY5Y neuroblastoma cells, while using LC-MS/MS analysis to identify multiple differentially expressed proteins in these cells. Among these differentially expressed proteins, we confirmed four proteins (ACTG1, ANP32E, CLTC, IPO8) that are differentially expressed under the administration of amisulpride.

Conclusion: Our data reveal novel insights into the role of amisulpride in modulating the differential expression of genes and proteins. These findings, which involve genes/proteins related to AP-1 transcription factor family gene regulation, cytoskeleton, histone binding activity, the intracellular trafficking of receptors and endocytosis of a variety of macromolecules, and nuclear localisation signal, are particularly significant as they shed light on the molecular underpinnings of the clinical efficacy of amisulpride and the pathogenesis of schizophrenia.