Neurobehavioral effect of chronic and bolus doses of methylmercury following prenatal exposure in C57BL/6 weanling mice

Liang, Jacky; Inskip, M. J.; Newhook, Deborah; Messier, Claude

doi:10.1016/j.ntt.2009.08.007

Cited by 25 publications

(16 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…That is, exposed animals showed no neurological signs, weight loss, reproductive toxicity, or changes in physical appearance even as they showed significant, if subtle, neurotoxicity as adults (Newland, 2012; Newland et al, 2008). Such sensitivity has been reported with auditory, visual, and somatosensory deficits in monkeys (Rice, 1996) and in behavioral studies with rodents (Bourdineaud et al, 2008; Bourdineaud et al, 2011; Castoldi et al, 2008; Liang et al, 2009; Montgomery et al, 2008; Newland et al, 2008; Onishchenko et al, 2008; Weiss et al, 2005) and are linked to disturbances in the development of the dopamine systems (Rasmussen and Newland, 2001; Reed and Newland, 2009). …”

Section: The Developmental Window Is Importantmentioning

confidence: 63%

A hypothesis about how early developmental methylmercury exposure disrupts behavior in adulthood

Newland

Reed

Rasmussen

2015

Behavioural Processes

View full text Add to dashboard Cite

Events that disrupt the early development of the nervous system have lifelong, irreversible behavioral consequences. The environmental contaminant, methylmercury (MeHg), impairs neural development with effects that are manifested well into adulthood and even into aging. Noting the sensitivity of the developing brain to MeHg, the current review advances an argument that one outcome of early MeHg exposure is a distortion in the processing of reinforcing consequences that results in impaired choice, poor inhibition of prepotent responding, and perseveration on discrimination reversals (in the absence of alteration of extradimensional shifts). Neurochemical correlates include increased sensitivity to dopamine agonists and decreased sensitivity to gamma-aminobutyric acid (GABA) agonists. This leads to a hypothesis that the prefrontal cortex or dopamine neurotransmission is especially sensitive to even subtle gestational MeHg exposure and suggests that public health assessments of MeHg based on intellectual performance may underestimate the impact of MeHg in public health. Finally, those interested in modeling neural development may benefit from MeHg as an experimental model.

show abstract

Section: The Developmental Window Is Importantmentioning

confidence: 63%

A hypothesis about how early developmental methylmercury exposure disrupts behavior in adulthood

Newland

Reed

Rasmussen

2015

Behavioural Processes

View full text Add to dashboard Cite

show abstract

“…For these reasons, the study focused on brain monoamine systems and behaviors known to be impacted by MeHg (Ceccatelli et al, 2013; Liang et al, 2009; Montgomery et al, 2008; Newland et al, 2013; Newland et al, 2004; Onishchenko et al, 2007; Peters et al, 2010; Yoshida et al, 2011) and/or mediated by brain monoamine systems (Carratu et al, 2006; Castoldi et al, 2006; Coccini et al, 2011; Farina et al, 2011). First, multiple examples of the effects of MeHg effects that were enhanced by PS, or occurring only under conditions of PS, i.e., being unmasked by PS, were observed, including changes in brain neurochemistry and in behavior, particularly in females.…”

Section: Discussionmentioning

confidence: 99%

“…In some, but not all (Davidson et al, 2011) cohorts of children, prenatal MeHg in children has been associated with neurocognitive deficits, including increased diagnosis of attention deficit hyperactivity disorder and attention-related behaviors (Boucher et al, 2012), impaired visual recognition memory (Oken et al, 2005; Sagiv et al, 2012), and cognition and IQ (intelligence quotient) reductions (Jedrychowski et al, 2007; Lederman et al, 2008; Oken et al, 2008). Experimental animal studies likewise show deficits resulting from prenatal MeHg exposures in corresponding behavioral domains including deficits in learning, discrimination/transition reversal and working memory, increased perseverative behavior and increased behaviors interpreted as anxiety (Ceccatelli et al, 2013; Liang et al, 2009; Montgomery et al, 2008; Newland et al, 2013; Newland et al, 2004; Onishchenko et al, 2007; Peters et al, 2010; Yoshida et al, 2011). …”

Section: Introductionmentioning

confidence: 99%

Sex-dependent and non-monotonic enhancement and unmasking of methylmercury neurotoxicity by prenatal stress

et al. 2014

View full text Add to dashboard Cite

Methylmercury (MeHg) and prenatal stress (PS) are risk factors for neurotoxicity that may co-occur in human populations. Because they also share biological substrates and can produce common behavioral deficits, this study examined their joint effects on behavioral and neurochemical effects in male and female rats. Dams had access to 0, 0.5 or 2.5ppm MeHg chloride drinking water from two weeks prior to breeding through weaning. Half of the dams in each of these treatment groups also underwent PS on gestational days 16–17. This yielded 6 groups/gender: 0-NS, 0-PS, 0.5-NS, 0.5-PS, 2.5-NS, and 2.5-PS. Behavioral testing began in young adulthood and included Fixed Interval (FI) schedule-controlled behavior, novel object recognition (NOR) and locomotor activity, behaviors previously demonstrated to be sensitive to MeHg and/or mediated by brain mesocorticolimbic dopamine glutamate systems targeted by both MeHg and PS. Behavioral deficits were more pronounced in females and included impaired NOR recognition memory only under conditions of combined MeHg and PS, while non-monotonic reductions in FI response rates occurred, with greatest effects at the 0.5ppm concentration; the less reduced 2.5ppm FI response rates were further reduced under conditions of PS (2.5-PS). Correspondingly, many neurochemical changes produced by MeHg were only seen under conditions of PS, particularly in striatum in males and in hippocampus and nucleus accumbens in females, regions of significance to the mediation of FI and NOR performance. Collectively these findings demonstrate sex-dependent and non-monotonic effects of developmental MeHg exposure that can be unmasked or enhanced by PS, particularly for behavioral outcomes in females but for both sexes in neurochemical changes, that were observed at MeHg exposure concentrations that did not influence either reproductive outcomes or maternal behavior. Thus, assessment of risks associated with MeHg may be underestimated in the absence of other extant risk factors with which it may share common substrates and effects.

show abstract

“…This is far below the doses of MeHg given to mice found in the literature. A literature survey of the recent articles dealing with MeHg contamination in mice through diet or drinking water these last 2 years, identifies the commonly-used daily doses which were in decreasing order of concentration: 5.4 [47], 2 [40], 1.4 [48], 1 [49,50], and 0.5 mg MeHg/kg body weight [51]. These concentrations are 5400- to 500-times greater than the contamination pressure we have used in the present study.…”

Section: Discussionmentioning

confidence: 99%

Effects of Methylmercury Contained in a Diet Mimicking the Wayana Amerindians Contamination through Fish Consumption: Mercury Accumulation, Metallothionein Induction, Gene Expression Variations, and Role of the Chemokine CCL2

Bourdineaud

Laclau

Maury-Brachet

et al. 2012

IJMS

View full text Add to dashboard Cite

Methylmercury (MeHg) is a potent neurotoxin, and human beings are mainly exposed to this pollutant through fish consumption. We addressed the question of whether a diet mimicking the fish consumption of Wayanas Amerindians from French Guiana could result in observable adverse effects in mice. Wayanas adult men are subjected to a mean mercurial dose of 7 g Hg/week/kg of body weight. We decided to supplement a vegetarian-based mice diet with 0.1% of lyophilized Hoplias aimara fish, which Wayanas are fond of and equivalent to the same dose as that afflicting the Wayanas Amerindians. Total mercury contents were 1.4 ± 0.2 and 5.4 ± 0.5 ng Hg/g of food pellets for the control and aimara diets, respectively. After 14 months of exposure, the body parts and tissues displaying the highest mercury concentration on a dry weight (dw) basis were hair (733 ng/g) and kidney (511 ng/g), followed by the liver (77 ng/g). Surprisingly, despite the fact that MeHg is a neurotoxic compound, the brain accumulated low levels of mercury (35 ng/g in the cortex). The metallothionein (MT) protein concentration only increased in those tissues (kidney, muscles) in which MeHg demethylation had occurred. This can be taken as a molecular sign of divalent mercurial contamination since only Hg2+ has been reported yet to induce MT accumulation in contaminated tissues. The suppression of the synthesis of the chemokine CCL2 in the corresponding knockout (KO) mice resulted in important changes in gene expression patterns in the liver and brain. After three months of exposure to an aimara-containing diet, eight of 10 genes selected (Sdhb, Cytb, Cox1, Sod1, Sod2, Mt2, Mdr1a and Bax) were repressed in wild-type mice liver whereas none presented a differential expression in KO Ccl2−/− mice. In the wild-type mice brain, six of 12 genes selected (Cytb, Cox1, Sod1, Sod2, Mdr1a and Bax) presented a stimulated expression, whereas all remained at the basal level of expression in KO Ccl2−/− mice. In the liver of aimara-fed mice, histological alterations were observed for an accumulated mercury concentration as low as 32 ng/g, dw, and metal deposits were observed within the cytoplasm of hepatic cells.

show abstract

Neurobehavioral effect of chronic and bolus doses of methylmercury following prenatal exposure in C57BL/6 weanling mice

Cited by 25 publications

References 32 publications

A hypothesis about how early developmental methylmercury exposure disrupts behavior in adulthood

A hypothesis about how early developmental methylmercury exposure disrupts behavior in adulthood

Sex-dependent and non-monotonic enhancement and unmasking of methylmercury neurotoxicity by prenatal stress

Effects of Methylmercury Contained in a Diet Mimicking the Wayana Amerindians Contamination through Fish Consumption: Mercury Accumulation, Metallothionein Induction, Gene Expression Variations, and Role of the Chemokine CCL2

Contact Info

Product

Resources

About