Methylmercury impairs motor function in early development and induces oxidative stress in cerebellar granule cells

Patel, Eshan U.; Reynolds, Mindy

doi:10.1016/j.toxlet.2013.08.002

Cited by 35 publications

(26 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Patients with Minamata disease typically exhibit ataxia, dysarthria, visual impair-ment, acoustic disturbance and hypesthesia (Harada, 1995). These symptoms are thought to be caused by damage to the central nervous system, and accordingly, the neurotoxic effects of MeHg have been studied primarily in the brain (Antunes Dos Santos et al, 2016;Costa et al, 2004;Unoki et al, 2018;Patel and Reynolds, 2013;Farina et al, 2011). Despite observations of peripheral nerve injury in humans, the main features and mechanisms of peripheral MeHg neurotoxicity remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Methylmercury-induced neural degeneration in rat dorsal root ganglion is associated with the accumulation of microglia/macrophages and the proliferation of Schwann cells

et al. 2019

View full text Add to dashboard Cite

Exposure to organic mercury, especially methylmercury (MeHg), causes Minamata disease, a severe chronic neurological disorder. Minamata disease predominantly affects the central nervous system, and therefore, studies on the mechanisms of MeHg neurotoxicity have focused primarily on the brain. Although the peripheral nervous system is also affected by the organometallic compound and shows signs of neural degeneration, the mechanisms of peripheral MeHg neurotoxicity remain unclear. In the present study, we performed quantitative immunohistochemical analyses of the dorsal root ganglion (DRG) and associated sensory and motor fibers to clarify the mechanisms of MeHg-induced peripheral neurotoxicity in Wistar rats. Methylmercury chloride (6.7 mg/kg/day) was orally administrated for 5 days, followed by 2 days without administration, and this cycle was repeated once again. Seven and 14 days after the beginning of MeHg exposure, rats were anesthetized, and their DRGs and sensory and motor nerve fibers were removed and processed for immunohistochemical analyses. The frozen sections were immunostained for neuronal, Schwann cell, microglial and macrophage markers. DRG sensory neuron somata and axons showed significant degeneration on day 14. At the same time, an accumulation of microglia and the infiltration of macrophages were observed in the DRGs and sensory nerve fibers. In addition, MeHg caused significant Schwann cell proliferation in the sensory nerve fibers. In comparison, there was no noticeable change in the motor fibers. Our findings suggest that in the peripheral nervous system, MeHg toxicity is associated with neurodegenerative changes to DRG sensory neurons and the induction of a neuroprotective and/or enhancement of neurodegenerative host response.

show abstract

Section: Introductionmentioning

confidence: 99%

Methylmercury-induced neural degeneration in rat dorsal root ganglion is associated with the accumulation of microglia/macrophages and the proliferation of Schwann cells

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Iraqi children intoxicated with MeHg in utero showed congenital abnormalities such as being born blind or deaf (Bakir et al, 1980). The literature suggests that MeHg can easily penetrate into the blood-brain barrier as it gets transported as MeHg-L-cysteine complex across this blood-brain barrier via large neutral amino acid transporters, system L (Bridges and Zalups, 2005), leading to neuronal dysfunction (Limke et al, 2004;Ceccatelli et al, 2010;Patel and Reynolds, 2013). Hydroxytyrosol (HT) is a major phenolic compound in olives and olive oil.…”

Section: Introductionmentioning

confidence: 99%

Hydroxytyrosol, a dietary phenolic compound forestalls the toxic effects of methylmercury-induced toxicity in IMR-32 human neuroblastoma cells

Mohan¹,

Das

Rao

2015

Environ. Toxicol.

View full text Add to dashboard Cite

This study demonstrates the protective potential of hydroxytyrosol (HT), an olive oil phenol, against methylmercury (MeHg)-induced neurotoxicity using IMR-32 human neuroblastoma cell line. HT inhibited MeHg-induced cytotoxicity and genotoxicity as confirmed by MTT, micronucleus, and comet assays. Cells preconditioned with HT showed reduction of MeHg-induced cellular oxidative stress along with the maintenance of glutathione, superoxide dismutase, glutathione-S-tranferase, and catalase. Fluorescence microscopy and DNA ladder assays indicated the inhibitory effect of HT against MeHg-induced apoptosis, which was further established by Western blotting. An effective concentration of 5 µM HT caused downregulation of p53, bax, cytochrome c, and caspase 3 and upregulation of prosurvival proteins including nuclear factor erythroid 2-related factor 2 (Nrf2) and metallothionein. This work indicates the cytoprotective potential of HT against MeHg-induced toxicity primarily by the lowering of oxidative stress, which may be endorsed to its antigenotoxic and antiapoptotic potential, in addition to its free radical scavenging ability. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1264-1275, 2016.

show abstract

“…Because of an observed elevated sensitivity in embryos, a number of studies have focused on examining the specific mechanisms underlying of MeHg’s effects on the developing nervous system at both the phenotypic and cellular molecular level (Patel and Reynolds 2013). In vivo invertebrate studies with physiologically relevant exposures have shown a link between MeHg induced activation of the Notch pathway and a failure in proper neuron migration, survival, and axon outgrowth during Drosophila development (Engel et al 2012, 2014; Rand et al 2008, 2009).…”

Section: Introductionmentioning

confidence: 99%

Methylmercury exposure during early Xenopus laevis development affects cell proliferation and death but not neural progenitor specification

Huyck

Nagarkar

Olsen

et al. 2015

Neurotoxicology and Teratology

View full text Add to dashboard Cite

Methylmercury (MeHg) is a widespread environmental toxin that preferentially and adversely affects developing organisms. To investigate the impact of MeHg toxicity on the formation of the vertebrate nervous system at physiologically relevant concentrations, we designed a graded phenotype scale for evaluating Xenopus laevis embryos exposed to MeHg in solution. Embryos displayed a range of abnormalities in response to MeHg, particularly in brain development, which is influenced by both MeHg concentration and the number of embryos per ml of exposure solution. A TC50 of ~50 μg/l and LC50 of ~100 μg/l were found when maintaining embryos at a density of one per ml, and both increased with increasing embryo density. In situ hybridization and microarray analysis showed no significant change in expression of early neural patterning genes including sox2, en2, or delta; however a noticeable decrease was observed in the terminal neural differentiation genes GAD and xGAT, but not xVGlut. PCNA, a marker for proliferating cells, was negatively correlated with MeHg dose, with a significant reduction in cell number in the forebrain and spinal cord of exposed embryos by tadpole stages. Conversely, the number of apoptotic cells in neural regions detected by a TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay was significantly increased. These results provide evidence that disruption of embryonic neural development by MeHg may not be directly due to a loss of neural progenitor specification and gene transcription, but to a more general decrease in cell proliferation and increase in cell death throughout the developing nervous system.

show abstract

Methylmercury impairs motor function in early development and induces oxidative stress in cerebellar granule cells

Cited by 35 publications

References 81 publications

Methylmercury-induced neural degeneration in rat dorsal root ganglion is associated with the accumulation of microglia/macrophages and the proliferation of Schwann cells

Methylmercury-induced neural degeneration in rat dorsal root ganglion is associated with the accumulation of microglia/macrophages and the proliferation of Schwann cells

Hydroxytyrosol, a dietary phenolic compound forestalls the toxic effects of methylmercury-induced toxicity in IMR-32 human neuroblastoma cells

Methylmercury exposure during early Xenopus laevis development affects cell proliferation and death but not neural progenitor specification

Contact Info

Product

Resources

About