Aldolase C and T helper 1 polarization in postpartum depression: a novel perspective on disease mechanisms.

Purpose

Postpartum depression (PPD) is common, yet its pathophysiology remains unclear and reliable early biomarkers are lacking.

Methods

Mendelian randomization, bioinformatics analyses, and animal experiments were integrated. A prenatal stress-induced rat model of PPD was established. Depressive-like behaviors were assessed using the open field and forced swim tests, and brain histopathology was examined by hematoxylin-eosin staining. Serum HPA-axis hormones, ALDOC, lactic acid, and Th1/Th2 cytokines were measured by ELISA. ALDOC was analyzed by Western blot. T-bet and GATA3 mRNA expression in peripheral blood mononuclear cells was detected by qRT-PCR, and the T-bet/GATA3 ratio was calculated.

Results

Sixteen overlapping genes were identified, suggesting the involvement of Th cells in PPD and highlighting ALDOC as a potential candidate biomarker associated with Th1-related immune alterations. PPD rats showed depressive-like behaviors and HPA-axis activation, with increased CRH and ACTH but unchanged CORT levels. ALDOC and lactic acid levels were significantly increased, accompanied by elevated Th1-related cytokines (IFN-γ, TNF-α, and IL-1β) and an increased IFN-γ/IL-4 ratio, whereas Th2-related cytokines showed no significant changes. Consistently, T-bet expression increased, GATA3 expression decreased, and the T-bet/GATA3 ratio was elevated, further supporting a possible Th1-skewed immune response. Brain histopathology showed cellular damage and reduced cell density. In the PFC, ALDOC upregulation was accompanied by increased pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), which may suggest coordinated central neuroinflammation and peripheral immune imbalance.

Conclusions

ALDOC may contribute to PPD pathogenesis by promoting Th1 polarization and inflammatory activation.