Brain Disorders and Chemical Pollutants: A Gap Junction Link?

Abstract

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.

Applicability of Scrape Loading-Dye Transfer Assay for Non-Genotoxic Carcinogen Testing

“…Prepared according to information from [27,30,31]. Impaired or dysregulated GJIC has been identified or implicated in the etiology of multiple diseases and pathologies [34,35]. With respect to its central signal integrating and tissue homeostatic function, GJIC dysregulation/untimely inhibition in normal cells has Gap junctions in homeostasis.…”

“…Prepared according to information from [27,30,31]. Impaired or dysregulated GJIC has been identified or implicated in the etiology of multiple diseases and pathologies [34,35]. With respect to its central signal integrating and tissue homeostatic function, GJIC dysregulation/untimely inhibition in normal cells has been connected to diseases involving disruption of tissue homeostasis, e.g., mitogenic signaling and proliferation, such as tumor-promoting stage of cancer and mechanisms of NGTxC [2,3,7,24,25].…”

Neurodevelopmental Disorders (NDD) Caused by Genomic Alterations of the Ubiquitin-Proteasome System (UPS): the Possible Contribution of Immune Dysregulation to Disease Pathogenesis

“…Brain pathologies such as NDD and/or ND are complex disorders which are caused for the most part by genetic and/or environmental factors ( Cardoso et al, 2019 ; Dunn et al, 2019 ). For instance, unquestionable risk factors for the development of NDD include prenatal asphyxia ( Adhikari and Rao, 2017 ) as well as exposure to ethanol ( Sokol et al, 2003 ), heavy metals ( Ijomone et al, 2020 ), and/or organic pollutants ( Mesnil et al, 2020 ). The genetic components of a large fraction of these psychiatric disorders are difficult to unravel since most of them are not necessarily Mendelian (dominant, recessive, or X-linked) and involve the participation of allelic variants in several genes ( Au et al, 2020 ; Savatt and Myers, 2021 ).…”

Is the Exposome Involved in Brain Disorders through the Serotoninergic System?

“…The developing nervous system of a fetus and newborn is susceptible to the deleterious effects of neurotoxic substances in our environment, and perinatal exposure could result in the later development of diseases [16]. From childhood up to adult life, because of their lipophilic properties, some of these pollutants are able to cross the BBB and reach the CNS [17]. This review presents the data that are contributing to establish a link between the effects of the exposome on the serotoninergic system and the increasing incidence of brain pathologies.…”