Altered PLCβ/IP/Ca Signaling Pathway Activated by GPRCs in Olfactory Neuronal Precursor Cells Derived from Patients Diagnosed with Schizophrenia.

: Schizophrenia (SZ) is a multifactorial chronic psychiatric disorder with a worldwide prevalence of 1%. Altered expression of PLCβ occurs in SZ patients, suggesting alterations in the PLCβ/IP/Ca signaling pathway. This cascade regulates critical cellular processes in all cell types, including the neuronal lineage; however, there is scarce evidence regarding the functionality of this transduction signaling in neuronal cells derived from SZ patients. : We evaluated the functionality of the PLCβ/IP/Ca pathway in olfactory neuronal precursor cells (hONPCs) obtained from SZ patients. : Cryopreserved hONPCs isolated from SZ patients and healthy subjects (HS) were thawed. The cellular types in subcultures were corroborated by immunodetection of the multipotency and lineage markers SOX-2, Musashi-1, nestin, and β-III tubulin. The PLCβ/IP/Ca pathway was activated by GPCR (G) ligands (ATP, UTP, serotonin, and epinephrine). In addition, PLCβ and IPR were directly stimulated by perfusing cells with the activators m-3M3FBS and ADA, respectively. Cytosolic Ca was measured by microfluorometry and by Ca imaging. The amount and subcellular distribution of the PLCβ1 and PLCβ3 isoforms were evaluated by confocal immunofluorescence. IP concentration was measured by ELISA. : The results show that the increase of cytosolic Ca triggered by GPCR ligands or directly through either PLCβ or IPR activation was significantly lower in SZ-derived hONPCs, regarding HS-derived cells. Moreover, the relative amount of the PLCβ1 and PLCβ3 isoforms and IP production stimulated with m-3M3FBS were reduced in SZ-derived cells. : Our results suggest an overall functional impairment in the PLCβ/IP/Ca signaling pathway in SZ-derived hONPCs.