Prenatal low-dose Bisphenol A exposure impacts cortical development via cAMP-PKA-CREB pathway in offspring

作者全名："Jiang, Chu; Guan, Jun; Tang, Xiangrong; Zhang, Yichun; Li, Xiangyu; Li, Yuting; Chen, Zhiheng; Zhang, Jing; Li, Jia-Da"

作者地址："[Jiang, Chu; Guan, Jun; Zhang, Yichun; Li, Xiangyu; Zhang, Jing; Li, Jia-Da] Cent South Univ, Ctr Med Genet, Sch Life Sci, Furong Lab, Changsha, Hunan, Peoples R China; [Jiang, Chu; Guan, Jun; Zhang, Yichun; Li, Xiangyu; Zhang, Jing; Li, Jia-Da] Hunan Key Lab Anim Models Human Dis, Changsha, Hunan, Peoples R China; [Jiang, Chu; Guan, Jun; Zhang, Yichun; Li, Xiangyu; Zhang, Jing; Li, Jia-Da] Hunan Key Lab Med Genet, Changsha, Hunan, Peoples R China; [Tang, Xiangrong] Chongqing Med Univ, Women & Childrens Hosp, Ctr Reprod Med, Chongqing, Peoples R China; [Li, Yuting; Chen, Zhiheng] Cent South Univ, Xiangya Hosp 3, Dept Pediat, Changsha, Peoples R China"

通信作者："Zhang, J; Li, JD (通讯作者)，Cent South Univ, Ctr Med Genet, Sch Life Sci, Furong Lab, Changsha, Hunan, Peoples R China.; Zhang, J; Li, JD (通讯作者)，Hunan Key Lab Anim Models Human Dis, Changsha, Hunan, Peoples R China.; Zhang, J; Li, JD (通讯作者)，Hunan Key Lab Med Genet, Changsha, Hunan, Peoples R China."

来源：FRONTIERS IN INTEGRATIVE NEUROSCIENCE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001294443300001

JCR分区：Q3

影响因子：3.5

年份：2024

卷号：18

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：BPA; prenatal low-dose exposure; neuronal proliferation; neuronal migration; cAMP-PKA-CREB pathway; manic-like behaviors

摘要："Bisphenol A (BPA) is a widely used plasticizer known to cause various disorders. Despite a global reduction in the use of BPA-containing products, prenatal exposure to low-dose BPA, even those below established safety limits, has been linked to neurological and behavioral deficits in childhood. The precise mechanisms underlying these effects remain unclear. In the present study, we observed a significant increase in the number of cortical neurons in offspring born to dams exposed to low-dose BPA during pregnancy. We also found that this prenatal exposure to low-dose BPA led to increased proliferation but reduced migration of cortical neurons. Transcriptomic analysis via RNA sequencing revealed an aberrant activation of the cAMP-PKA-CREB pathway in offspring exposed to BPA. The use of H89, a selective PKA inhibitor, effectively rescued the deficits in both proliferation and migration of cortical neurons. Furthermore, offspring from dams exposed to low-dose BPA exhibited manic-like behaviors, including hyperactivity, anti-depressant-like responses, and reduced anxiety. While H89 normalized hyperactivity, it didn't affect the other behavioral changes. These results suggest that the overactivation of PKA plays a causative role in BPA-induced changes in neuronal development. Our data also indicate that manic-like behaviors induced by prenatal low-dose BPA exposure may be influenced by both altered neuronal development and abnormal PKA signaling in adulthood."

基金机构："National Natural Science Foundation of China [82070815, 31972913, 32371218, 81770780]; Key Research and Development Programs from Hunan Province [2021DK2001]; Guangdong Key Project in ""Development of New Tools for Diagnosis and Treatment of Autism"" [2018B030335001]; Postdoctoral Fellowship Program of CPSF [GZB20240877]; Hunan Provincial Natural Science Foundation [2024JJ6552]"

基金资助正文："The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (grant numbers: 82070815, 31972913, 32371218, and 81770780), Key Research and Development Programs from Hunan Province (grant number: 2021DK2001), the Guangdong Key Project in ""Development of New Tools for Diagnosis and Treatment of Autism"" (grant number: 2018B030335001), the Postdoctoral Fellowship Program of CPSF (grant number: GZB20240877), and the Hunan Provincial Natural Science Foundation (grant number: 2024JJ6552)."