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, Syntaxin1a 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.

Icariin ameliorates learning and memory impairments through ERK/CaMKIIα/CREB signaling and HPA axis in prenatally stressed female offspring.

BACKGROUND: Prenatal stress (PS) leads to a wide variety of behavioral and emotional aberration observed in later life, particularly in the impairment of spatial learning and memory in offspring. Icariin (ICA) is a naturally occurring furanocoumarin and exhibits many pharmacological properties, including potent improvement on learning and memory. PURPOSE: We pretend to investigate the improvement of ICA on learning and memory impairment in PS. METHODS: Female PS offspring rats were used to explore the effects of ICA on learning and memory impairment. After 28 days of ICA (20, 40 and 80 mg/kg/day) treatment, we measured Morris water maze and 8-Arm Maze, the HPA axis and the related pathway in the hippocampus. RESULTS: We reported that ICA ameliorated the spatial learning and memory and working memory impairment in the female offspring rats. Correspondingly, ICA prevented adverse changes in the dendritic morphology of CA3 pyramidal neurons in the hippocampus. ICA significantly decreased the serum adrenocorticotropin, corticotropin-releasing hormone and corticosterone levels in offspring rats exposed to PS, associated with increased GR expression. Additionally, ICA treatment significantly increased the neurogranin (Ng) and c-fos protein expression of hippocampus in the offspring rats. Furthermore, the protein of relative content of p-EKR/ERK, p-CaMKIIα/CaMKIIα, p-CREB/CREB were remarkably increased after ICA treatment in the offspring rats. CONCLUSION: Taken together, ICA may be an effective therapeutic for learning and memory dysfunction in female offspring exposed to PS, its neuroprotective effect was mediated in part by normalizing the HPA axis and up-regulating of ERK/CaMKIIα/CREB signaling, Ng and c-fos protein.