Arsenic metabolites affect expression of the neurofilament and tau genes: An in-vitro study into the mechanism of arsenic neurotoxicity

Vahidnia, A.; Straaten, R.J.H.M. van der; Romijn, Fred P.H.T.M.; Pelt, Johannes van; Voet, Gijsbert B. van der; Wolff, Frederik A. de

doi:10.1016/j.tiv.2007.04.007

Cited by 36 publications

(18 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although exposure to arsenic has been associated with risk of carcinogenesis and cardiovascular disorders, increasing incidences of cognitive deficits and neurobehavioral changes in the population specially in growing children is a matter of concern (Siripitayakunkit et al, 1999; Chen et al, 2011;Hamadani et al, 2011;Abir et al, 2012). As a result, epidemiological and experimental studies have been carried out extensively to assess the impact and potential of arsenic on different targets in the brain in an attempt to understand the mechanism of its neurotoxicity (Piao et al, 2005;Vahidnia et al, 2007;Singh et al, 2011). Recently, we found that early life exposure to arsenic at low doses resulted to cause cholinergic alterations in the brain associated with impaired learning and memory in rats (Chandravanshi et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Early life arsenic exposure and brain dopaminergic alterations in rats

Chandravanshi

Shukla

Sultana

et al. 2014

Intl J of Devlp Neuroscience

View full text Add to dashboard Cite

Recently, we found that early life exposure to arsenic at low doses resulted to cause brain cholinergic deficits and exhibited a trend of recovery on withdrawal of arsenic exposure. In continuation to this, the present study has been carried out to assess the impact of low level arsenic exposure on brain dopaminergic system and associated behavior in developing rats and investigate if neurobehavioral changes are recovered or persistent. Early life exposure (PD22-PD59) to arsenic (2 or 4 mg/kg body weight, p.o.) in rats resulted to increase the motor activity on PD60, compared to controls. The hyperactivity in arsenic exposed rats was found to be linked with increase in the binding of DA-D2 receptors (38%, 56%), mRNA expression of DAR-D2 receptor gene (68%, 97%) and expression of tyrosine hydroxylase protein (1.93, 2.73-fold) in the corpus striatum as compared to controls on PD60. Exposure to arsenic enhanced generation of ROS (47%, 84%) and was associated with decrease in the mitochondrial membrane potential (13.3%, 15.33%), activity of mitochondrial complexes and increased oxidative stress. Disruption in the expression of pro-apoptotic, anti-apoptotic and stress marker proteins was also distinct in the corpus striatum of arsenic exposed rats. The severity of changes in the behavioral and neurochemical endpoints were found to persist in rats exposed to arsenic at high dose and exhibited a trend of recovery at low dose on withdrawal of arsenic exposure on PD90. Early life arsenic exposure appears to be critical and vulnerable as development of dopamine receptors continues during this period.

show abstract

Section: Discussionmentioning

confidence: 99%

Early life arsenic exposure and brain dopaminergic alterations in rats

Chandravanshi

Shukla

Sultana

et al. 2014

Intl J of Devlp Neuroscience

View full text Add to dashboard Cite

show abstract

“…In contrast to inorganic arsenic, methylarsonate and dimethylarsinate (≥0.3 µM 24 or 48 hours incubation) decreased the gene expression of neurofilament proteins in vitro (Vahidnia et al 2007b), but not gene expression of p35. Similar to arsenite, methylarsonite and dimethylarsinite (10, 30 µM, 4 hours incubation) increase p35 gene expression and p35 cleavage to p25 (Vahidnia et al, 2008b).…”

Section: Organic Arsenicmentioning

confidence: 95%

Scientific Opinion on Arsenic in Food

2009

EFSA Journal

877

220

View full text Add to dashboard Cite

The EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) assessed the risks to human health related to the presence of arsenic in food. More than 100,000 occurrence data on arsenic in food were considered with approximately 98 % reported as total arsenic. Making a number of assumptions for the contribution of inorganic arsenic to total arsenic, the inorganic arsenic exposure from food and water across 19 European countries, using lower bound and upper bound concentrations, has been estimated to range from 0.13 to 0.56 µg/kg bodyweight (b.w.) per day for average consumers, and from 0.37 to 1.22 µg/kg b.w. per day for 95 th percentile consumers. Dietary exposure to inorganic arsenic for children under three years of age is in general estimated to be from 2 to 3-fold that of adults. The CONTAM Panel concluded that the provisional tolerable weekly intake (PTWI) of 15 µg/kg b.w. established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) is no longer appropriate as data had shown that inorganic arsenic causes cancer of the lung and urinary bladder in addition to skin, and that a range of adverse effects had been reported at exposures lower than those reviewed by the JECFA. The CONTAM Panel modelled the dose-response data from key for providing consumption information and calculating exposure, the partners of the EFSA project on the "Individual food consumption data and exposure" coordinated by Ghent University (Department of Public Health, University Hospital, Ghent University, Belgium), and RIKILT (Institute of Food Safety, Wageningen, The Netherlands) for the accessibility of the exposure assessment tools. 4 Table of contents shows now the fourth level of subheadings. 5 An error in the interpretation of the total number of the population in the study of Rahman et al. (2006a) was discovered (Table 41). The BMDL was recalculated and as a consequence it was not considered a potential reference point. The text in the opinion, Table 43 and Appendix were revised accordingly. In addition, the header of the "total number of cases" was replaced by "total number of individuals" in Tables 40-42 and the erroneous units were corrected to µg/L in the text below SUMMARYArsenic is a metalloid that occurs in different inorganic and organic forms, which are found in the environment both from natural occurrence and from anthropogenic activity. The inorganic forms of arsenic are more toxic as compared to the organic arsenic but so far most of the occurrence data in food collected in the framework of official food control are still reported as total arsenic without differentiating the various arsenic species. The need for speciation data is evident because several investigations have shown that especially in seafood most of the arsenic is present in organic forms that are less toxic. Consequently, a risk assessment not taking into account the different species but considering total arsenic as being present exclusively as inorganic arsenic would lead to a considerable overestimation of the health risk rel...

show abstract

“…ii) increased APP expression and B amyloid formation [34], iii) impaired synaptic transmission [35], increased tau protein phosphorylation [36,37], and reticulum endoplasmic stress induction [38].…”

Section: Discussionmentioning

confidence: 99%

Cortical Astrocytes Acutely Exposed to the Monomethylarsonous Acid (MMAIII) Show Increased Pro-inflammatory Cytokines Gene Expression that is Consistent with APP and BACE-1: Over-expression

et al. 2016

View full text Add to dashboard Cite

Long-term exposure to inorganic arsenic (iAs) through drinking water has been associated with cognitive impairment in children and adults; however, the related pathogenic mechanisms have not been completely described. Increased or chronic inflammation in the brain is linked to impaired cognition and neurodegeneration; iAs induces strong inflammatory responses in several cells, but this effect has been poorly evaluated in central nervous system (CNS) cells.Because astrocytes are the most abundant cells in the CNS and play a critical role in brain homeostasis, including regulation of the inflammatory response, any functional impairment in them can be deleterious for the brain. We propose that iAs could induce cognitive impairment through inflammatory response activation in astrocytes. In the present work, rat cortical astrocytes were acutely exposed in vitro to the monomethylated metabolite of iAs (MMA III ), which accumulates in glial cells without compromising cell viability. MMA III LD 50 in astrocytes was 10.52 μM, however, exposure to sub-toxic MMA III concentrations (50 to 1000 nM) significantly increased IL-1β, IL-6, TNF-α, COX-2, and MIF-1 gene expression. These effects were consistent with amyloid precursor protein (APP) and β-secretase (BACE-1) increased gene expression, mainly for those MMA III concentrations that also induced TNF-α over-expression. Other effects of MMA III on cortical astrocytes included increased proliferative and metabolic activity. All tested MMA III concentrations led to an inhibition of intracellular lactate dehydrogenase (LDH) activity. Results suggest that MMA III induces important metabolic and functional changes in astrocytes that may affect brain homeostasis and that inflammation may play a major role in cognitive impairment-related pathogenicity in As-exposed populations.

show abstract

Arsenic metabolites affect expression of the neurofilament and tau genes: An in-vitro study into the mechanism of arsenic neurotoxicity

Cited by 36 publications

References 23 publications

Early life arsenic exposure and brain dopaminergic alterations in rats

Early life arsenic exposure and brain dopaminergic alterations in rats

Scientific Opinion on Arsenic in Food

Cortical Astrocytes Acutely Exposed to the Monomethylarsonous Acid (MMAIII) Show Increased Pro-inflammatory Cytokines Gene Expression that is Consistent with APP and BACE-1: Over-expression

Contact Info

Product

Resources

About