Mesnil Marc, Defamie Norah, Naus Christian, Sarrouilhe Denis
Laboratoire STIM, ERL7003 CNRS-Université de Poitiers, 1 rue G. Bonnet-TSA 51 106, 86073 Poitiers, CEDEX 09, France.
Professor Emeritus, Faculty of Medicine, Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T1Z3, Canada.
Biomolecules. 2020 Dec 31;11(1):51. doi: 10.3390/biom11010051.
The incidence of brain pathologies has increased during last decades. Better diagnosis (autism spectrum disorders) and longer life expectancy (Parkinson's disease, Alzheimer's disease) partly explain this increase, while emerging data suggest pollutant exposures as a possible but still underestimated cause of major brain disorders. Taking into account that the brain parenchyma is rich in gap junctions and that most pollutants inhibit their function; brain disorders might be the consequence of gap-junctional alterations due to long-term exposures to pollutants. In this article, this hypothesis is addressed through three complementary aspects: (1) the gap-junctional organization and connexin expression in brain parenchyma and their function; (2) the effect of major pollutants (pesticides, bisphenol A, phthalates, heavy metals, airborne particles, etc.) on gap-junctional and connexin functions; (3) a description of the major brain disorders categorized as neurodevelopmental (autism spectrum disorders, attention deficit hyperactivity disorders, epilepsy), neurobehavioral (migraines, major depressive disorders), neurodegenerative (Parkinson's and Alzheimer's diseases) and cancers (glioma), in which both connexin dysfunction and pollutant involvement have been described. Based on these different aspects, the possible involvement of pollutant-inhibited gap junctions in brain disorders is discussed for prenatal and postnatal exposures.
在过去几十年中，脑部病变的发病率有所上升。更好的诊断（自闭症谱系障碍）和更长的预期寿命（帕金森病、阿尔茨海默病）部分解释了这种上升趋势，而新出现的数据表明，接触污染物可能是主要脑部疾病的一个原因，但仍未得到充分重视。考虑到脑实质富含缝隙连接，且大多数污染物会抑制其功能；脑部疾病可能是长期接触污染物导致缝隙连接改变的结果。在本文中，将通过三个互补的方面来探讨这一假设：（1）脑实质中缝隙连接的组织和连接蛋白的表达及其功能；（2）主要污染物（农药、双酚A、邻苯二甲酸盐、重金属、空气颗粒物等）对缝隙连接和连接蛋白功能的影响；（3）对主要脑部疾病的描述，这些疾病分为神经发育性疾病（自闭症谱系障碍、注意力缺陷多动障碍、癫痫）、神经行为性疾病（偏头痛、重度抑郁症）、神经退行性疾病（帕金森病和阿尔茨海默病）和癌症（胶质瘤），其中均已描述了连接蛋白功能障碍和污染物的参与情况。基于这些不同方面，讨论了产前和产后接触污染物导致缝隙连接受抑制在脑部疾病中的可能作用。
