Increases in the Number of Reactive Glia in the Visual Cortex of Macaca fascicularis Following Subclinical Long-Term Methyl Mercury Exposure

Charleston, Jay S.; Bolender, Robert P.; Mottet, N. Karle; Body, R.L.; Vahter, Marie; Burbacher, Thomas M.

doi:10.1006/taap.1994.1244

Cited by 123 publications

(109 citation statements)

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“…While MeHg can directly cause damage to neurons, numerous studies have established a prominent role for astrocytes in mediating MeHg neurotoxicity [23,36]. The evidence includes observations that MeHg preferentially accumulate in astrocytes [5,18,34] and inhibits uptake systems for glutamate and cysteine transport, both of which will compromise glutathione (GSH) synthesis and redox status in astrocytes [2,16,30,61,62,63]. Furthermore, MeHg causes the activation of cytosolic phospholipase A 2 (cPLA 2 ), leading to arachidonic acid release and further inhibition of glutamate transporters and neuronal dysfunction [6,8].…”

Section: Introductionmentioning

confidence: 99%

Methylmercury induces oxidative injury, alterations in permeability and glutamine transport in cultured astrocytes

Yin¹,

Milatović²,

Aschner³

et al. 2007

Brain Research

161

100

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The neurotoxicity of high levels of methylmercury (MeHg) is well established both in humans and experimental animals. Astrocytes accumulate MeHg and play a prominent role in mediating MeHg toxicity in the central nervous system (CNS). Although the precise mechanisms of MeHg neurotoxicity are ill-defined, oxidative stress and altered mitochondrial and cell membrane permeability appear to be critical factors in its pathogenesis. The present study examined the effects of MeHg treatment on oxidative injury, mitochondrial inner membrane potential, glutamine uptake and expression of glutamine transporters in primary astrocyte cultures. MeHg caused a significant increase in F 2 -isoprostanes (F 2 -IsoPs), lipid peroxidation biomarkers of oxidative damage, in astrocyte cultures treated with 5 or 10 μ M MeHg for 1 or 6 hours. Consistent with this observation, MeHg induced a concentration-dependant reduction in the inner mitochondrial membrane potential (ΔΨm), as assessed by the potentiometric dye, tetramethylrhodamine ethyl ester (TMRE). Our results demonstrate that ΔΨ m is a very sensitive endpoint for MeHg toxicity, since significant reductions were observed after only 1 h exposure to concentrations of MeHg as low as 1 μ M. MeHg pretreatment (1, 5 and 10 μ M) for 30 min also inhibited the net uptake of glutamine ( 3 H-glutamine) measured at 1 min and 5 min. Expression of the mRNA coding the glutamine transporters, SNAT3/SN1 and ASCT2, was inhibited only at the highest (10 μ M) MeHg concentration, suggesting that the reduction in glutamine uptake observed after 30 min treatment with lower concentrations of MeHg (1 and 5 μ M) was not due to inhibition of transcription. Taken together, these studies demonstrate that MeHg exposure is associated with increased mitochondrial membrane permeability, alterations in glutamine/glutamate cycling, increased ROS formation and consequent oxidative injury. Ultimately, MeHg initiates multiple additive or synergistic disruptive mechanisms that lead to cellular dysfunction and cell death.Please send request for reprints to Michael Aschner, Ph.D.,

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Section: Introductionmentioning

confidence: 99%

Methylmercury induces oxidative injury, alterations in permeability and glutamine transport in cultured astrocytes

Yin¹,

Milatović²,

Aschner³

et al. 2007

Brain Research

161

100

View full text Add to dashboard Cite

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“…Asimismo, otros estudios recientes han mostrado evidencias de gliosis asociada a la pérdida de células de Purkinje y un marcado proceso neuroinflamatorio difuso cerebral en niños con autismo ( [128][129][130][131] ). Precisamente, la persistencia de Hg inorgánico en el cerebro de los animales de experimentación, luego de haber sido expuestos a metilHg, timerosal o Hg inorgánico, ha sido asociada a un incremento significativo de las células de la microglía, disminución del número de astrocitos y afectación de las células de Purkinje ( 52,[132][133][134] ). Finalmente, diversos estudios neuropatológicos han mostrado anormalidades en la organización de la citoarquitectura de la corteza cerebral y estructuras subcorticales en pacientes con autismo, sugiriéndose que dichos defectos en la maduración neuronal y en la organización cortical pueden ser los responsables de los problemas neurológicos vistos en esta enfermedad ( 128,[135][136][137] ).…”

Section: Resultsunclassified

Efectos neurotóxicos del timerosal, a dosis de vacuna, sobre el encéfalo y el desarrollo en hámsteres de 7 días de nacidos

et al. 2013

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“…In human: Vennetti et al, 2006 in monkey (Macaca fascicularis) : Charleston et al, 1994: Charleston et al, , 1996 in rat: Little et al, 2012;Zurich et al, 2002;Eskes et al, 2002in mouse: Liu et al, 2012in zebrafish: Xu et al, 2014 …”

Section: A63 Evidence Supporting Taxonomic Applicabilitymentioning

confidence: 99%

Investigation into experimental toxicological properties of plant protection products having a potential link to Parkinson's disease and childhood leukaemia†

Ockleford¹,

Adriaanse²,

Berny³

et al. 2017

EFS2

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In 2013, EFSA published a literature review on epidemiological studies linking exposure to pesticides and human health outcome. As a follow up, the EFSA Panel on Plant Protection Products and their residues (PPR Panel) was requested to investigate the plausible involvement of pesticide exposure as a risk factor for Parkinson's disease (PD) and childhood leukaemia (CHL). A systematic literature review on PD and CHL and mode of actions for pesticides was published by EFSA in 2016 and used as background documentation. The Panel used the Adverse Outcome Pathway (AOP) conceptual framework to define the biological plausibility in relation to epidemiological studies by means of identification of specific symptoms of the diseases as AO. The AOP combines multiple information and provides knowledge of biological pathways, highlights species differences and similarities, identifies research needs and supports regulatory decisions. In this context, the AOP approach could help in organising the available experimental knowledge to assess biological plausibility by describing the link between a molecular initiating event (MIE) and the AO through a series of biologically plausible and essential key events (KEs). As the AOP is chemically agnostic, tool chemical compounds were selected to empirically support the response and temporal concordance of the key event relationships (KERs). Three qualitative and one putative AOP were developed by the Panel using the results obtained. The Panel supports the use of the AOP framework to scientifically and transparently explore the biological plausibility of the association between pesticide exposure and human health outcomes, identify data gaps, define a tailored testing strategy and suggests an AOP's informed Integrated Approach for Testing and Assessment (IATA).

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Increases in the Number of Reactive Glia in the Visual Cortex of Macaca fascicularis Following Subclinical Long-Term Methyl Mercury Exposure

Cited by 123 publications

References 0 publications

Methylmercury induces oxidative injury, alterations in permeability and glutamine transport in cultured astrocytes

Methylmercury induces oxidative injury, alterations in permeability and glutamine transport in cultured astrocytes

Efectos neurotóxicos del timerosal, a dosis de vacuna, sobre el encéfalo y el desarrollo en hámsteres de 7 días de nacidos

Investigation into experimental toxicological properties of plant protection products having a potential link to Parkinson's disease and childhood leukaemia†

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