Human-Induced Pluripotent Stem Cells are a Unique Approach for Modeling Schizophrenia: Calcium Homeostasis

Schizophrenia (SZ) is a widespread, chronic, and developmental mental disorder resulting from disruption in neural connections. SZ causes social and occupational disabilities, including a wide range of mental disorders that can lead to improper behaviors. Over 1% of the world's population has been affected by SZ which is mostly characterized by distortions in thinking, perception, emotion, language, and behavior. This disorder has been accompanied by other mental problems, such as anxiety, depression, or addiction. An emerging hypothesis suggests a central role of dysregulation of Ca2+ homeostasis in the pathophysiology of SZ. Numerous intracellular signals initiated by Ca2+ ions are responsible for modulating neuronal excitability, information processing, and cognition. Ca2+ signaling and homeostasis impairment in glutamatergic, GABAergic, and dopaminergic neurons are early characteristics of SZ. The discovery of human induced pluripotent stem cells (iPSC) offers a novel and promising patient-specific cellular disease model for SZ. However, the central role of Ca2+ homeostasis and the detailed mechanisms in SZ using the iPSCs model still needs further investigation. Here, we explore the current understanding of Ca2+ homeostasis and iPSCs model-based studies in SZ, as well as potential future directions to identify robust and valid cellular phenotypes for drug testing and development.

The iPSCs model is a powerful tool for elucidating the mechanism of Ca2+ homeostasis, understanding SZ pathophysiology, and drug development.