RT journal article
T1 Cellular and proteomic differences associated with lithium response in olfactory neuroepithelium cells of bipolar disorder patients
A1 Hidalgo Figueroa, María
A1 Delgado Sequera, Alejandra Cristina
A1 Pérez Ramos, Anaid
A1 Durán Ruiz, María del Carmen
A1 Romero-López-Alberca, Cristina
A1 Pérez Revuelta, José Ildefonso
A1 Márquez Estefenn, Ingrid Catherine
A1 García Mompo, Clara
A1 Villagrán Moreno, José María
A1 Berrocoso Domínguez, Esther María
A2 BiomedicinaBiotecnología y Salud Pública
A2 Neurociencias
A2 Psicología
K1 Bipolar disorder
K1 Cytoskeleton
K1 Lithium
K1 Olfactory neuroepithelium
K1 Proteomics
AB Background Lithium is a first-line treatment for bipolar disorder (BD), but only 30% of patients respond satisfactorilyto monotherapy, and the biological basis for this variability remains unclear. This study aimed to identify potentialbiomarkers and therapeutic targets by analyzing olfactory neuroepithelium (ONE) cells from BD lithium nonresponders (BDNR), responders (BDR), and control subjects.Methods Immunofluorescence and proteomic analyses of ONE cells were conducted. Blood samples were examinedto improve accessibility for clinical applications.Results Immunofluorescence and proteomic analyses of ONE cells revealed that BDNR cells exhibited impairedadhesion capacity, which was restored by lithium treatment in vitro. However, BDNR cells also showed significantalterations in cell morphology and cytoskeletal organization that were unaffected by lithium. Proteomic analysisidentified significant changes in pathways associated with “cell morphology,” with CDN2A highlighted as a key protein.In BDR cells, lithium treatment restored adhesion capacity but failed to reverse migration deficits. Proteomic analysisof BDR ONE cells identified differentially expressed proteins linked to neurotransmitter release, synaptic function,and mitochondrial activity, many of which were significantly modulated by lithium. Additionally, peripheral bloodmononuclear cells from BDR patients displayed lower levels of RHOC protein, mirroring reductions seen in ONE BDRcells treated with lithium.Conclusions This study underscores cellular and proteomic differences between BDNR and BDR cells, with lithiumexerting pronounced effects on BDR cells while having limited impact on BDNR cells. These findings advanceour understanding of lithium responsiveness in BD and point to potential biomarkers and therapeutic targets forpersonalized treatment approaches.
PB Springer Nature
SN 1528-3658
YR 2025
FD 2025-09-26
LK http://hdl.handle.net/10498/38364
UL http://hdl.handle.net/10498/38364
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 09-nov-2026