Distinct patterns of cell adhesion, migration, and morphology in olfactory neuroepithelium cells of bipolar disorder patients

Abstract

Background: Bipolar disorder (BD) is a severe, chronic mental illness that remains difficult to diagnose due to the lack of specific biomarkers, relying primarily on clinical assessments. Early diagnosis and treatment are essential for improving prognosis and lowering suicide risk. This study aimed to identify biomarkers and therapeutic targets by utilizing olfactory neuroepithelium (ONE) cells from patients with BD and controls. Methods: Immunofluorescence of ONE cells, along with proteomic and RNA sequencing analyses, was performed to investigate cytoskeletal changes and pathways involved in cell adhesion, movement, and morphology. Additionally, potential biomarkers were investigated in blood samples to improve clinical accessibility. Results: Thus, according to functional assays, ONE cells derived from BD patients exhibited decreased substrate adhesion, reduced cell migration, and morphological changes compared to control cells. In addition, proteomic and RNAseq analyses in ONE cells and peripheral blood mononuclear cells (PBMCs) revealed alterations in pathways such as RhoA/PAK/Integrin and Actin Cytoskeleton Signaling, as well as significant changes in inflammatory and immunological pathways. AUROC analysis identified proteins like PTK2 as potential diagnostic biomarkers, showing altered expression in both ONE cells and PBMCs. PTK2 RNA expression correlated with distinct morphological traits in BD ONE cells. Conclusions: In summary, this study identified cytoskeletal alterations, reduced adhesion, and disrupted migration patterns in BD ONE cells, highlighting molecular mechanisms underlying these changes and emphasizing PTK2's role as a potential diagnostic biomarker for BD.