Xing Xing Zheng1, Yi Wei Chen1, Yi Song Yue1, Ying Chun Li1, Si Zhe Xia1, Yang Li1, Huan Huan Deng1, Jiao He1, Yan Jun Cao2. 1. Biomedicine Key Laboratory of Shaanxi Province, school of pharmacy, Northwest University, Xi'an, PR China; Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi'an, PR China. 2. Biomedicine Key Laboratory of Shaanxi Province, school of pharmacy, Northwest University, Xi'an, PR China; Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi'an, PR China. Electronic address: cao2014@nwu.edu.cn.
Abstract
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.
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.