PMID- 32380187 OWN - NLM STAT- MEDLINE DCOM- 20210929 LR - 20231213 IS - 1873-2747 (Electronic) IS - 0361-9230 (Linking) VI - 161 DP - 2020 Aug TI - Impairment of learning and memory induced by perinatal exposure to BPA is associated with ERalpha-mediated alterations of synaptic plasticity and PKC/ERK/CREB signaling pathway in offspring rats. PG - 43-54 LID - S0361-9230(20)30052-6 [pii] LID - 10.1016/j.brainresbull.2020.04.023 [doi] AB - The effect of bisphenol A (BPA) on learning and memory has attracted much attention recently, but its underlying mechanism remains unclear. We aimed to investigate whether the impairment of learning and memory induced by perinatal exposure to BPA was associated with the hippocampal estrogen receptor alpha (ERalpha)-mediated synaptic plasticity and PKC/ERK/CREB signaling pathway in different sex offspring rats. Pregnant Sprague-Dawley rats were treated with BPA (1 and 10 mug/mL) through drinking water from gestational day (GD) 6 to postnatal day (PND) 21. After weaning, offspring drank BPA-free water until PND 56. Morris water maze, placement and object recognition, and step-down passive avoidance task were performed. The serum estradiol (E2) levels, histopathology of hippocampus, and the expression of learning and memory related proteins were measured. The results showed that spatial and recognition memory were impaired in BPA-exposed female and male offspring, but the impaired passive avoidance memory presented only in males, not in females. The serum E2 levels were increased in BPA-exposed females and males. BPA altered the morphology and quantity of hippocampal neurons. The levels of ERalpha, NMDA receptor subunit 2B (NR2B), p-NR2B, AMPA receptor 1 (GluA1), p-GluA1, PSD-95, synapsin I, PKC, p-ERK and p-CREB protein expression were decreased in BPA exposed females and males, and there were interactions of sex x BPA exposure in ERalpha, p-NR2B and p-ERK levels. These findings suggested that perinatal exposure to BPA has sex-specific effects on learning and memory, which is associated with ERalpha-mediated impairment of synaptic plasticity and down-regulation of PKC/ERK/CREB signaling pathway. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Wu, Dan AU - Wu D AD - Department of Child and Adolescent Health, School of Public Health, China Medical University, Shenyang 110122, China. Electronic address: wudan@cmu.edu.cn. FAU - Wu, Fengjuan AU - Wu F AD - Department of Child and Adolescent Health, School of Public Health, China Medical University, Shenyang 110122, China. Electronic address: 18524430655@163.com. FAU - Lin, Ren AU - Lin R AD - Department of Child and Adolescent Health, School of Public Health, China Medical University, Shenyang 110122, China. Electronic address: 15804066682@163.com. FAU - Meng, Yuan AU - Meng Y AD - Department of Child and Adolescent Health, School of Public Health, China Medical University, Shenyang 110122, China. Electronic address: yuanyuan_max@163.com. FAU - Wei, Wei AU - Wei W AD - Department of Child and Adolescent Health, School of Public Health, China Medical University, Shenyang 110122, China. Electronic address: wwei@cmu.edu.cn. FAU - Sun, Qi AU - Sun Q AD - Department of Child and Adolescent Health, School of Public Health, China Medical University, Shenyang 110122, China. Electronic address: sunqi@cmu.edu.com. FAU - Jia, Lihong AU - Jia L AD - Department of Child and Adolescent Health, School of Public Health, China Medical University, Shenyang 110122, China. Electronic address: lhjia@cmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200505 PL - United States TA - Brain Res Bull JT - Brain research bulletin JID - 7605818 RN - 0 (Benzhydryl Compounds) RN - 0 (Creb1 protein, rat) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Estrogen Receptor alpha) RN - 0 (Estrogens, Non-Steroidal) RN - 0 (Phenols) RN - MLT3645I99 (bisphenol A) SB - IM MH - Animals MH - Benzhydryl Compounds/*toxicity MH - Cyclic AMP Response Element-Binding Protein/antagonists & inhibitors/*metabolism MH - Dose-Response Relationship, Drug MH - Estrogen Receptor alpha/antagonists & inhibitors/*metabolism MH - Estrogens, Non-Steroidal/toxicity MH - Female MH - MAP Kinase Signaling System/drug effects/*physiology MH - Male MH - Maze Learning/drug effects/physiology MH - Memory Disorders/chemically induced/*metabolism MH - Neuronal Plasticity/drug effects/physiology MH - Phenols/*toxicity MH - Pregnancy MH - Prenatal Exposure Delayed Effects/chemically induced/*metabolism MH - Rats MH - Rats, Sprague-Dawley OTO - NOTNLM OT - Bisphenol A OT - Estrogen receptor alpha OT - Learning and memory OT - PKC/ERK/CREB pathway OT - Synaptic plasticity COIS- Declaration of Competing Interest The authors declare that they have no conflict of interest. EDAT- 2020/05/08 06:00 MHDA- 2021/09/30 06:00 CRDT- 2020/05/08 06:00 PHST- 2020/01/16 00:00 [received] PHST- 2020/04/17 00:00 [revised] PHST- 2020/04/27 00:00 [accepted] PHST- 2020/05/08 06:00 [pubmed] PHST- 2021/09/30 06:00 [medline] PHST- 2020/05/08 06:00 [entrez] AID - S0361-9230(20)30052-6 [pii] AID - 10.1016/j.brainresbull.2020.04.023 [doi] PST - ppublish SO - Brain Res Bull. 2020 Aug;161:43-54. doi: 10.1016/j.brainresbull.2020.04.023. Epub 2020 May 5.