Epigenetics and Methylmercury-Induced Neurotoxicity, Evidence from Experimental Studies

Abstract

MeHg is an environmental neurotoxin that can adversely affect the development of the nervous system. The molecular integrity of chromatin in the nucleus is an important target of MeHg. Low levels of MeHg trigger epigenetic mechanisms that may be involved in long-lasting and transgenerational neurotoxicity after exposure. Emerging evidence has shown that these mechanisms include histone modification, siRNA, and DNA methylation. The MeHg-induced inhibition of neurodifferentiation and neurogenesis are mechanistically associated with epigenetic alterations in critical genes, such as neurotrophin brain-derived neurotrophic factor (BDNF). Further, MeHg exposure has been shown to alter the activity and/or expression of the upstream regulators of chromatin structure, including histone deacetylases (HDACs) and DNA methyltransferase (DNMTs), which may trigger permanent alterations in histone modifications and DNA methylation. MeHg-exposure also alters several species of miRNA that are associated with neurodevelopment. Genetic studies in the C. elegans model of MeHg-induced toxicity proposes a potential interplay between exogenous RNAi and antioxidant defense. In this review, we discuss the molecular basis for MeHg exposure-induced alterations in chromatin structure and the roles of histone modifications, siRNA, and DNA methylation in MeHg-induced neurotoxic effects.

Reproductive-Toxicity-Related Endpoints in C. elegans Are Consistent with Reduced Concern for Dimethylarsinic Acid Exposure Relative to Inorganic Arsenic

“…Rodent and C. elegans assays have demonstrated epigenetic alterations, including to histone modifications, directly induced by NaAsO 2 and meHgCl exposures, as well as in their offspring [ 71 , 72 , 73 , 74 , 75 , 76 ]. Multi-generational studies on zebrafish and mice have demonstrated the long-term effects of mercury exposure passed down for multiple generations, indicating the potential effects on the epigenome [ 77 , 78 , 79 ]. However, most of these studies were not specific to reproductive endpoints and did not compare different forms of arsenic and/or mercury.…”

Emerging insights into the impacts of heavy metals exposure on health, reproductive and productive performance of livestock

“…Diagnosis of toxic metal poisoning in cattle also involves testing milk, an indirect indicator of environmental pollution (Pšenková et al, 2020). Toxic metals predominantly accumulate in internal organs making it feasible to establish standard levels in the body (Ke et al, 2023). Diagnosis and control of contamination in animal feed ensure the safety of human food and health.…”

“…Further, Pb disrupts calcium signaling pathways by interfering with calcium-dependent processes that affects neurotransmitter release and synaptic plasticity ( Cory-Slechta et al, 2016 ). Hg impairs mitochondrial function and energy metabolism, causing cellular dysfunction and apoptosis ( Ke et al, 2023 ). Moreover, by disrupting neurotransmitter signaling, Hg interferes with the function of ion channels and neurotransmitter transporters, contributing to neurotoxicity ( Novo et al, 2021 ).…”

“…Toxic metals predominantly accumulate in internal organs making it feasible to establish standard levels in the body ( Ke et al, 2023 ). Diagnosis and control of contamination in animal feed ensure the safety of human food and health.…”

Effects of Endocrine-Disrupting Heavy Metals on Human Health

“…For example, inorganic Hg in water and sediment can synthesize MeHg under the action of microorganisms [61]. The emerging evidence for Hg-induced toxicity is mainly neurotoxicity, reproductive toxicity, histone modification, siRNA and DNA damage, and methylation [62][63][64][65][66]. In addition, prenatal and postnatal exposure to Hg is significantly associated with testosterone levels and Tanner stage > 1 in children [67].…”