Paeoniflorin ameliorates depressive-like behavior in prenatally stressed offspring by restoring the HPA axis- and glucocorticoid receptor- associated dysfunction

Background: Prenatal stress (PS) can increase the risk of nervous, endocrine and metabolic diseases and induce depression in offspring. Paeoniflorin (PA) is an amorphous glucoside isolated from the aqueous extract of roots of the peony plant (Paeonia lactiflora Pall.) and exerts various pharmacological effects in the nervous system. Methods: Male prenatally stressed offspring were used to investigate the antidepression-like effects and possible mechanism of PA. We measured animal behavior, HPA axis, Nissil staining, and Ng expression. Additionally, we assessed the modulation of hippocampal glucocorticoid receptors (GR) nuclear translocation and SNARE complex expression by western blotting. Results: The results showed that administration of PA (15, 30, and 60 mg/kg/day, i.g.) for 28 days markedly increased sucrose intake and decreased the immobility time and the total number of crossings, center crossings, rearing, and grooming in male PS offspring. Moreover, PA significantly reduced the serum corticosterone (CORT), adrenocorticotropin (ACTH), corticotropin-releasing hormone (CRH) and hippocampal glutamate (Glu) levels in male PS offspring, which were stimulated by an increase of GR nuclear translocation. Furthermore, PA markedly increased neurogranin (Ng) protein expression in the hippocampus CA3 region in offspring. PA also markedly decreased hippocampal Glu by inhibiting SNAP25, VAMP2, Syntaxinl a and related protein expression; SNARE complex formation; and EAAT2/3, NR1, NR2A, and FKBP5 protein expression. Conclusions: Taken together, the results of this study show that PA has antidepression-like effects in male PS offspring, partially due to the HPA axis, GR dysfunction and Glu transport system.