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Imperatorin ameliorates learning and memory deficits through BDNF / TrkB and ERK / CaMKIIα / CREB signaling in prenatally‐stressed female offspring
Author(s) -
Zheng Xing X.,
Zhang Kai Y.,
Li Ying C.,
Chen Yi W.,
Yue Yi S.,
Xia Si Z.,
Li Yang,
Deng Huan H.,
Jing Hui L.,
Cao Yan J.
Publication year - 2020
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6692
Subject(s) - creb , offspring , endocrinology , tropomyosin receptor kinase b , medicine , mapk/erk pathway , hippocampus , hippocampal formation , receptor , biology , signal transduction , neurotrophic factors , microbiology and biotechnology , transcription factor , pregnancy , biochemistry , genetics , gene
Prenatal stress (PS) can lead to impaired spatial learning and memory in offspring. Imperatorin (IMP) is a naturally occurring furanocoumarin with many pharmacological properties. However, the effects of IMP on cognitive impairment induced by PS and the underlying molecular mechanisms remain unclear. We investigated the protective effect of IMP treatment after PS on learning and memory deficits in female offspring at postnatal 60 days. After treating prenatally‐stressed offspring with IMP (15 and 30 mg/kg) for 28 days, we found that IMP increased body weight and ameliorated spatial learning and memory and working memory deficits in female offspring rats. Meanwhile, hippocampal Glu and serum corticosterone levels in prenatally‐stressed offspring were significantly decreased after IMP administration. Additionally, IMP treatment significantly increased BDNF, TrkB, CaMKII , and CREB mRNA expression in the hippocampus of offspring rats. Furthermore, PS‐mediated induction of RKIP protein and mRNA expression and glucocorticoid receptor protein expression in the hippocampus of offspring rats were significantly decreased by IMP treatment, and the protein expression of BDNF and TrkB and relative levels of p‐EKR/ERK, p‐CaMKIIα/CaMKIIα, and p‐CREB/CREB were remarkably increased after IMP treatment. Taken together, IMP can ameliorate PS‐induced learning and memory deficits through BDNF/TrkB and ERK/CaMKIIα/CREB signaling pathway and hypothalamic–pituitary–adrenal axis.