Upregulation of proBDNF/p75NTR signaling in lymphocytes and its correlation with inflammatory markers in patients with major depression

Major depressive disorder (MDD) is a serious mental disorder with unclear pathogenesis. ProBDNF is the precursor protein of brain derived neurotrophic factor (BDNF) expressed in the central nervous system and peripheral tissues. Previous studies showed that the blood levels of both proBDNF and inflammatory cytokines in MDD were increased, but which blood cell types express proBDNF and its receptors is not known. Furthermore, the relationship between proBDNF/p75NTR and inflammatory cytokines in peripheral blood of MDD is unclear. Peripheral blood mononuclear cells (PBMCs) and serum were obtained from depressive patients (n=32) and normal donors (n=20). Using flow cytometry analysis, we examined which blood cells express proBDNF and its receptors. Q-PCR and Western blots showed proBDNF, p75NTR and sortilin levels were significantly increased in PBMCs from MDD patients compared with that from the normal donors. Flow cytometry studies showed that proBDNF and p75NTR were present mainly in CD4+ and CD8+ T-cells and CD19+ B cells. The number of proBDNF and p75NTR positive CD4+, CD8+ T cells and CD19+ B cells from MDD patients was increased and subsequently reversed after therapeutic management. Inflammatory cytokines in PBMC from MDD patients were also increased. The levels of IL-1β and IL-10 were also positively correlated with the major depression scores, while the levels of TNF-α and IL-6 were negatively correlated with the major depression scores. Intriguingly, the levels of sortilin was positively correlated with IL-1β. Our data also suggest that proBDNF/p75NTR/sortilin signaling pathway in T and B cells may serve as biomarkers for MDD.