Abstract
The 18 kDa translocator protein (TSPO) is primarily localized in the outer mitochondrial membrane of steroid-synthesizing cells in the central and peripheral nervous systems. One of the protein’s main functions is transporting substrate cholesterol into the mitochondria in a prerequisite process for steroid synthesis. Clinical trials have indicated that TSPO ligands might be valuable in treating some neuropathies and psychopathies. However, limited information is known about the role of TSPO in postpartum depression (PPD). The TSPO ligand ZBD-2, a derivative of XBD173, was synthesized in our laboratory. Behavioral tests, enzyme linked immunosorbent assay, and Western blot were employed to evaluate ZBD-2’s efficacy against PPD and to elucidate the potential underlying molecular mechanism. The TSPO levels significantly decreased in the basolateral amygdala of PPD models. After treatment for 2 weeks, ZBD-2 alleviated depression-like behaviors and enhanced the TSPO level in a PPD animal model. The underlying mechanisms of ZBD-2 were related to regulate the hypothalamic-pituitary-adrenal axis, enhance 5-HT and BDNF secretion, and maintain the excitatory and inhibitory synaptic protein expression to normal levels. Our results directly confirm that ZBD-2 exerts a therapeutic effect on PPD, which provides a new target for anti-PPD drug development.
Highlights
Postpartum depression (PPD), a widespread mental disorder, occurs in women soon after giving birth [1]
The postpartum depression (PPD) models showed decreased numbers of entries and time spent in open arms in the Elevated plus maze (EPM) test (percent time spent in open arms: F(6,35) = 18.47, P < 0.001, least significant difference (LSD) test; percent number of entries in open arms: F(6,35) = 19.09, P < 0.001, LSD test, Fig. 1c and d)
The effects of ZBD-2 were blocked by PK11195, which indicated that ZBD-2 takes effect through activating translocator protein (TSPO)
Summary
Postpartum depression (PPD), a widespread mental disorder, occurs in women soon after giving birth [1]. Data have shown that approximately 40% of new mothers develop moderate to severe depression, and symptoms include sadness and hopelessness [2]. PPD is well known to negatively influence the offspring, which may acquire deficits in cognitive and social interaction, as well as emotional disorders [3]. Peptide and steroid hormones dramatically fluctuate during pregnancy and the postpartum period; these changes may exacerbate symptoms in vulnerable women. In women at risk for depression, many symptoms attack during the period encompassing large variations in estradiol and progesterone [4]
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