Altered PLCβ/IP[sub.3]/Ca[sup.2+] Signaling Pathway Activated by GPRCs in Olfactory Neuronal Precursor Cells Derived from Patients Diagnosed with Schizophrenia

• Published in: Biomedicines 2024-10, Vol.12 (10)
• 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: Article
• Language: English
• Subjects: Analysis; Care and treatment; Cryopreservation of organs, tissues, etc; Diagnosis; Genetic aspects; Methods; Neural transmission; Phospholipases; Schizophrenia
• 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/IP[sub.3] /Ca[sup.2+] 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/IP[sub.3] /Ca[sup.2+] 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/IP[sub.3] /Ca[sup.2+] pathway was activated by GPCR (G[sub.q] ) ligands (ATP, UTP, serotonin, and epinephrine). In addition, PLCβ and IP[sub.3] R were directly stimulated by perfusing cells with the activators m-3M3FBS and ADA, respectively. Cytosolic Ca[sup.2+] was measured by microfluorometry and by Ca[sup.2+] imaging. The amount and subcellular distribution of the PLCβ1 and PLCβ3 isoforms were evaluated by confocal immunofluorescence. IP[sub.3] concentration was measured by ELISA. Results : The results show that the increase of cytosolic Ca[sup.2+] triggered by GPCR ligands or directly through either PLCβ or IP[sub.3] R activation was significantly lower in SZ-derived hONPCs, regarding HS-derived cells. Moreover, the relative amount of the PLCβ1 and PLCβ3 isoforms and IP[sub.3] production stimulated with m-3M3FBS were reduced in SZ-derived cells. Conclusions : Our results suggest an overall functional impairment in the PLCβ/IP[sub.3] /Ca[sup.2+] signaling pathway in SZ-derived hONPCs.