BACKGROUND

Schizophrenia (SZ), a chronic and widespread brain disorder, presents with complex etiology and pathogenesis that remain inadequately understood. Despite the absence of a universally recognized endophenotype, peripheral blood mononuclear cells (PBMCs) serve as a robust model for investigating intracellular alterations linked to SZ.

AIM

To preliminarily investigate potential pathogenic mechanisms and identify novel biomarkers for SZ.

METHODS

PBMCs from SZ patients were subjected to integrative transcriptomic and proteomic analyses to uncover differentially expressed genes (DEGs) and differentially expressed proteins while mapping putative disease-associated signaling pathways. Key findings were validated using western blot (WB) and real-time fluorescence quantitative PCR (RT-qPCR). RNAi-lentivirus was employed to transfect rat hippocampal CA1 neurons in vitro, with subsequent verification of target gene expression RT-qPCR. The levels of neuronal conduction proteins, including calmodulin-dependent protein kinase II (caMKII), CREB, and BDNF, were assessed through WB. Apoptosis was quantified by flow cytometry, while cell proliferation and viability were evaluated using the Cell Counting Kit-8 assay.

RESULTS

The integration of transcriptomic and proteomic analyses identified 6079 co-expressed genes, among which 25 DEGs were significantly altered between the SZ group and healthy controls. Notably, haptoglobin (), lactotransferrin (), and exhibited marked upregulation. KEGG pathway enrichment analysis implicated neuroactive ligand-receptor interaction pathways in disease pathogenesis. Clinical sample validation demonstrated elevated protein and mRNA levels of , , and in the SZ group compared to controls. WB analysis of all clinical samples further corroborated the significant upregulation of . In hippocampal CA1 neurons transfected with lentivirus, reduced expression was accompanied by increased levels of CaMKII, CREB, and BDNF, enhanced cell viability, and reduced apoptosis.

CONCLUSION

may suppress neural cell proliferation in SZ patients modulation of the CaMKII-CREB-BDNF signaling pathway.