Oxidative Stress in Methylmercury-Induced Cell Toxicity.

Methylmercury (MeHg) is a hazardous environmental pollutant, which elicits significant toxicity in humans. The accumulation of MeHg through the daily consumption of large predatory fish poses potential health risks, and the central nervous system (CNS) is the primary target of toxicity. Despite well-described neurobehavioral effects (i.e., motor impairment), the mechanisms of MeHg-induced toxicity are not completely understood. However, several lines of evidence point out the oxidative stress as an important molecular mechanism in MeHg-induced intoxication. Indeed, MeHg is a soft electrophile that preferentially interacts with nucleophilic groups (mainly thiols and selenols) from proteins and low-molecular-weight molecules. Such interaction contributes to the occurrence of oxidative stress, which can produce damage by several interacting mechanisms, impairing the function of various molecules (i.e., proteins, lipids, and nucleic acids), potentially resulting in modulation of different cellular signal transduction pathways. This review summarizes the general aspects regarding the interaction between MeHg with regulators of the antioxidant response system that are rich in thiol and selenol groups such as glutathione (GSH), and the selenoenzymes thioredoxin reductase (TrxR) and glutathione peroxidase (Gpx). A particular attention is directed towards the role of the PI3K/Akt signaling pathway and the nuclear transcription factor NF-E2-related factor 2 (Nrf2) in MeHg-induced redox imbalance.

BXD recombinant inbred strains participate in social preference, anxiety and depression behaviors along sex-differences in cytokines and tactile allodynia.

Depression and anxiety are the most common psychiatric disorders, representing a major public health concern. Dysregulation of oxidative and inflammatory systems may be associated with psychiatric disorders, such as depression and anxiety. Due to the need to find appropriate animal models to the understanding of such disorders, we queried whether 2 BXD recombinant inbred (RI) mice strains (BXD21/TyJ RI and BXD84/RwwJ RI mice) and C57BL/6 wild-type mice show differential performance in depression and anxiety related behaviors and biomarkers. Specifically, we assessed social preference, elevated plus maze, forced swim, and Von Frey tests at 3-4 months-of-age, as well as activation of cytokines and antioxidant mRNA levels in the cortex at 7 months-of-age. We report that (1) the BXD84/RwwJ RI strain exhibits anxiety disorder and social avoidance-like behavior (2) BXD21/TyJ RI strain shows a resistance to depression illness, and (3) sex-dependent cytokine profiles and allodynia with elevated inflammatory activity were inherent to male BXD21/TyJ RI mice. In conclusion, we provide novel data in favor of the use of BXD recombinant inbred mice to further understand anxiety and depression disorders.

Methylmercury and brain development: A review of recent literature.

Methylmercury (MeHg) is a potent environmental pollutant, which elicits significant toxicity in humans. The central nervous system (CNS) is the primary target of toxicity, and is particularly vulnerable during development. Maternal exposure to MeHg via consumption of fish and seafood can have irreversible effects on the neurobehavioral development of children, even in the absence of symptoms in the mother. It is well documented that developmental MeHg exposure may lead to neurological alterations, including cognitive and motor dysfunction. The neurotoxic effects of MeHg on the developing brain have been extensively studied. The mechanism of toxicity, however, is not fully understood. No single process can explain the multitude of effects observed in MeHg-induced neurotoxicity. This review summarizes the most current knowledge on the effects of MeHg during nervous system development considering both, in vitro and in vivo experimental models. Considerable attention was directed towards the role of glutamate and calcium dyshomeostasis, mitochondrial dysfunction, as well as the effects of MeHg on cytoskeletal components/regulators.