Altered PLCβ/IP3/Ca2+ Signaling Pathway Activated by GPRCs in Olfactory Neuronal Precursor Cells Derived from Patients Diagnosed with Schizophrenia

• Published in: Biomedicines Vol. 12; no. 10; p. 2343
• Main Authors: Sánchez-Florentino, Zuly A., Romero-Martínez, Bianca S., Flores-Soto, Edgar, Montaño, Luis M., Sommer, Bettina, Valdés-Tovar, Marcela, Argueta, Jesús, Calixto, Eduardo, Aquino-Gálvez, Arnoldo, Castillejos-López, Manuel, Serrano, Héctor, Gomez-Verjan, Juan C., López-Riquelme, Germán O., Benítez-King, Gloria A., Jaimez, Ruth, Solís-Chagoyán, Héctor
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 15.10.2024; MDPI
• Subjects: Alzheimer's disease; Antibodies; Calcium imaging; calcium signaling; Calcium signalling; Cell activation; Cell culture; Cognitive ability; Cryopreservation; Disease; Dopamine; Enzyme-linked immunosorbent assay; Enzymes; G protein-coupled receptors; Genes; human olfactory neuronal stem cells; Immunofluorescence; Inositol 1,4,5-trisphosphate receptors; IP3; Isoforms; Ligands; Mental disorders; Musashi protein; Nestin; PLCβ; Proteins; Schizophrenia; Signal transduction; Stem cells; Subcultures; Tubulin; United States > US
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines12102343

Background: 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/IP3/Ca2+ 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. Objective: We evaluated the functionality of the PLCβ/IP3/Ca2+ pathway in olfactory neuronal precursor cells (hONPCs) obtained from SZ patients. Methods: 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/IP3/Ca2+ pathway was activated by GPCR (Gq) ligands (ATP, UTP, serotonin, and epinephrine). In addition, PLCβ and IP3R were directly stimulated by perfusing cells with the activators m-3M3FBS and ADA, respectively. Cytosolic Ca2+ was measured by microfluorometry and by Ca2+ imaging. The amount and subcellular distribution of the PLCβ1 and PLCβ3 isoforms were evaluated by confocal immunofluorescence. IP3 concentration was measured by ELISA. Results: The results show that the increase of cytosolic Ca2+ triggered by GPCR ligands or directly through either PLCβ or IP3R activation was significantly lower in SZ-derived hONPCs, regarding HS-derived cells. Moreover, the relative amount of the PLCβ1 and PLCβ3 isoforms and IP3 production stimulated with m-3M3FBS were reduced in SZ-derived cells. Conclusions: Our results suggest an overall functional impairment in the PLCβ/IP3/Ca2+ signaling pathway in SZ-derived hONPCs.