Background: Induced pluripotent stem cell (iPSC) based neuronal differentiation is
valuable for studying neuropsychiatric disorders and pharmacological mechanisms at
the cellular level. We aimed to examine the effects of typical and atypical antipsychotics
on human iPSC-derived neural progenitor cells (NPCs). Methods: Proliferation and neurite
outgrowth were measured by live cell imaging, and gene expression levels related to
neuronal identity were analyzed by RT-QPCR and immunocytochemistry during differentiation
into hippocampal dentate gyrus granule cells following treatment of low- and high-dose
antipsychotics (haloperidol, olanzapine, and risperidone). Results: Antipsychotics
did not modify the growth properties of NPCs after 3 days of treatment. However, the
characteristics of neurite outgrowth changed significantly in response to haloperidol
and olanzapine. After three weeks of differentiation, mRNA expression levels of the
selected neuronal markers increased (except for MAP2), while antipsychotics caused
only subtle changes. Additionally, we found no changes in MAP2 or GFAP protein expression
levels as a result of antipsychotic treatment. Conclusions: Altogether, antipsychotic
medications promoted neurogenesis in vitro by influencing neurite outgrowth rather
than changing cell survival or gene expression. This study provides insights into
the effects of antipsychotics on neuronal differentiation and highlights the importance
of considering neurite outgrowth as a potential target of action.
