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

• Published in: Biomedicine & pharmacotherapy Vol. 117; p. 109077
• Main Authors: Zheng, Xing xing, Chen, Yi wei, Yue, Yi song, Li, Ying chun, Xia, Si zhe, Li, Yang, Deng, Huan huan, He, Jiao, Cao, Yan jun
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.09.2019; Elsevier
• Subjects: Animals; Calcium-Calmodulin-Dependent Protein Kinase Kinase - metabolism; CREB; Cyclic AMP Response Element-Binding Protein - metabolism; Disease Models, Animal; Female; Flavonoids - pharmacology; Hippocampus - drug effects; Hippocampus - metabolism; HPA axis; Hypothalamo-Hypophyseal System - drug effects; Hypothalamo-Hypophyseal System - metabolism; Icariin; Learning and memory; Male; MAP Kinase Signaling System - drug effects; Maze Learning - drug effects; Memory - drug effects; Memory Disorders - drug therapy; Memory Disorders - metabolism; Pituitary-Adrenal System - drug effects; Pituitary-Adrenal System - metabolism; Pregnancy; Prenatal Exposure Delayed Effects - drug therapy; Prenatal Exposure Delayed Effects - metabolism; Prenatal stress; Pyramidal Cells - drug effects; Pyramidal Cells - metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction - drug effects; Spatial Learning - drug effects; Stress, Psychological - drug therapy; Stress, Psychological - metabolism; Learning and memory; Icariin; MWM; PS; ICA; ACTH; LTP; HPA axis; GR; Glu; CORT; CaMKII; CREB; CRH; Ng; GC; ERK; Prenatal stress
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2019.109077

[Display omitted] •Icariin (ICA) protects against learning/memory impairments in female offspring exposed to prenatal stress (PS).•ICA decreases levels of serum adrenocorticotropin, corticotropin releasing hormone and corticosterone in female offspring exposed to PS.•ICA ameliorates PS-induced cognitive impairments may be depended on HPA axis and EKR/CaMKⅡα/CREB/c-fos pathway. 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. We pretend to investigate the improvement of ICA on learning and memory impairment in PS. 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. 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. 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.