Embryonic exposure to thimerosal, an organomercury compound, causes abnormal early development of serotonergic neurons

Ida-Eto, Michiru; Oyabu, Akiko; Ohkawara, Takeshi; Tashiro, Yasura; Narita, Naoko; Narita, Minoru

doi:10.1016/j.neulet.2011.05.053

Cited by 15 publications

(8 citation statements)

References 21 publications

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“…Evidence from animal studies demonstrates the neurodevelopmental impact of prenatal [37, 38] and perinatal exposure to vaccine-EtHg [39, 40]; these studies included infants of several species (mice, rats, and macaques) and suggest that the cumulative effects of TCV-Hg could lead to cognitive and social deficits and delayed acquisition of reflexes. Because this literature is very recent, it has not yet modeled the wide spectrum of human infant diversity and the full interaction with other neurotoxicants [41].…”

Section: Discussionmentioning

confidence: 99%

Neurodevelopment of Amazonian Infants: Antenatal and Postnatal Exposure to Methyl- and Ethylmercury

Dórea

Marques

Isejima

2012

Journal of Biomedicine and Biotechnology

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Neurodevelopment as Gesell development scores (GDSs) in relation to mercury exposure in infants (<6 months of age) of one urban center and two rural villages, respectively, of fisherman and cassiterite miners. Mean total hair-Hg (HHg) concentrations of infants from Itapuã (3.95 ± 1.8 ppm) were statistically (P = 0.0001) different from those of infants from Porto Velho (3.84 ± 5.5 ppm) and Bom Futuro (1.85 ± 0.9 ppm). Differences in vaccine coverage among these populations resulted in significantly higher (P = 0.0001) mean ethylmercury (EtHg) exposure in urban infants (150 μg) than in infants from either village (41.67 μg, Itapuã; 42.39 μg, Bom Futuro). There was an inverse significant (Spearman r = −0.2300; P = 0.0376) correlation between HHg and GDS for infants from Porto Velho, but not for the rural infants from Bom Futuro (Spearman r = 0.1336; P = 0.0862) and Itapuã (Spearman r = 0.1666; P = 0.5182). Logistic regression applied to variables above or below the median GDS showed that EtHg exposure (estimated probability = −0.0157; P = 0.0070) and breastfeeding score (estimated probability = −0.0066; P = 0.0536) score were significantly associated with GDS. Conclusion. In nurslings whose mothers are exposed to different levels of fish-MeHg (HHg), a higher score of neurological development at six months was negatively associated with exposure to additional TCV-EtHg. Results should be interpreted with caution because of unaccounted variables.

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Section: Discussionmentioning

confidence: 99%

Neurodevelopment of Amazonian Infants: Antenatal and Postnatal Exposure to Methyl- and Ethylmercury

Dórea

Marques

Isejima

2012

Journal of Biomedicine and Biotechnology

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“…Similarly, there is also an increase in the number of serotonergic neurons in the brain in autism. Azmitia et al [152] examined serotonin (5-HT) axons that were immunoreactive to a serotonin transporter (5-HTT) antibody in a number of postmortem brains from children and adults with autism and found that stained axons at all ages studied indicated that the number of serotonin axons was increased in both pathways and terminal regions in the cortex from autism donors.…”

Section: Research Evidencementioning

confidence: 99%

Thimerosal Exposure and the Role of Sulfation Chemistry and Thiol Availability in Autism

Kern

Haley

Geier

et al. 2013

IJERPH

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Autism spectrum disorder (ASD) is a neurological disorder in which a significant number of the children experience a developmental regression characterized by a loss of previously acquired skills and abilities. Typically reported are losses of verbal, nonverbal, and social abilities. Several recent studies suggest that children diagnosed with an ASD have abnormal sulfation chemistry, limited thiol availability, and decreased glutathione (GSH) reserve capacity, resulting in a compromised oxidation/reduction (redox) and detoxification capacity. Research indicates that the availability of thiols, particularly GSH, can influence the effects of thimerosal (TM) and other mercury (Hg) compounds. TM is an organomercurial compound (49.55% Hg by weight) that has been, and continues to be, used as a preservative in many childhood vaccines, particularly in developing countries. Thiol-modulating mechanisms affecting the cytotoxicity of TM have been identified. Importantly, the emergence of ASD symptoms post-6 months of age temporally follows the administration of many childhood vaccines. The purpose of the present critical review is provide mechanistic insight regarding how limited thiol availability, abnormal sulfation chemistry, and decreased GSH reserve capacity in children with an ASD could make them more susceptible to the toxic effects of TM routinely administered as part of mandated childhood immunization schedules.

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“…Our results indicate that early As‐induced impairments in the 5‐HTnergic system may affect the further development of the central nervous system. DNTs induced by other chemicals, including alcohol, valproic acid and thimerosal, an organomercury compound, resulting in alterations in the early 5‐HT system (Dufour‐Rainfray et al, 2010; Ida‐Eto et al, 2011; Kuwagata et al, 2009; Zhou et al, 2008). Therefore, the abnormal early development of 5‐HTnergic neurons induced by As may be an important mechanism in DNT.…”

Section: Discussionmentioning

confidence: 99%

“…of As to induce cell death in fetal brains may be due to its dosage, period of exposure, fetal developmental stage, and/or difference in antioxidant potential between in vitro and in vivo conditions. At GD16 rat fetal brain, monoaminergic system such as catecholaminergic and serotonergic systems is one of the most important endpoints as well as the neuroepithelium in the cortex to estimate effects of chemicals on early developing brain because this system arises in the first development of the nervous system, and disrupted development of monoaminergic system will lead to affect later development of the nervous system (Dufour-Rainfray et al, 2010;Ida-Eto et al, 2011;Kuwagata et al, 2009;Zhou et al, 2008). In this study, prenatal exposure to As did not affect the numbers of TH-positive neurons in the midbrain (nucleus) and striatum (projection area), despite exposure occurring during a period of active development of dopamine (DA) neurons, indicating that prenatal As exposure did not affect early development of DA neurons.…”

Section: Discussionmentioning

confidence: 99%

“…Analysis of dorsal (C) and median (D) raphe separately showed that 5-HT positive areas in each group did not differ from controls, indicating that the decreased in 5-HT positive areas following exposure to As was caused by As exposure, not by maternal stress. an organomercury compound, resulting in alterations in the early 5-HT system (Dufour-Rainfray et al, 2010;Ida-Eto et al, 2011;Kuwagata et al, 2009;Zhou et al, 2008). Therefore, the abnormal early development of 5-HTnergic neurons induced by As may be an important mechanism in DNT.…”

Section: Discussionmentioning

confidence: 99%

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Prenatal sodium arsenite affects early development of serotonergic neurons in the fetal rat brain

Senuma

Mori

Ogawa

et al. 2014

Intl J of Devlp Neuroscience

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Prenatal arsenite exposure has been associated with developmental disorders in children, including reduced IQ and language abnormalities. Animal experiments have also shown that exposure to arsenite during development induced developmental neurotoxicity after birth. However, the evidence is not enough, and the mechanism is poorly understood, especially on the exposure during early brain development. This study assessed effects of sodium (meta) arsenite shortly after exposure on early developing fetal rat brains. Pregnant rats were administered 50 mg/L arsenite in their drinking water or 20 mg/kg arsenite orally using a gastric tube, on gestational days (GD) 9-15. Fetal brains were examined on GD16. Pregnant rats administered 20 mg/kg arsenite showed reductions in maternal body weight gain and food consumption during treatment, but not with 50 mg/L arsenite. Arsenite did not affect fetal development, as determined by body weight, mortality and brain size. Arsenite also did not induce excessive cell death or affect neural cell division in any region of the fetal neuroepithelium. Thyrosine hydroxylase immunohistochemistry revealed no difference in the distribution of catecholaminergic neurons between fetuses of arsenite treated and control rats. However, reductions in the number of serotonin positive cells in the fetal median and dorsal raphe nuclei were observed following maternal treatment with 20mg/kg arsenite. Image analysis showed that the serotonin positive areas decreased in all fetal mid- and hind-brain areas without altering distribution patterns. Maternal stress induced by arsenite toxicity did not alter fetal development. These results suggest that arsenite-induced neurodevelopmental toxicity involves defects in the early development of the serotonin nervous system.

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Embryonic exposure to thimerosal, an organomercury compound, causes abnormal early development of serotonergic neurons

Cited by 15 publications

References 21 publications

Neurodevelopment of Amazonian Infants: Antenatal and Postnatal Exposure to Methyl- and Ethylmercury

Neurodevelopment of Amazonian Infants: Antenatal and Postnatal Exposure to Methyl- and Ethylmercury

Thimerosal Exposure and the Role of Sulfation Chemistry and Thiol Availability in Autism

Prenatal sodium arsenite affects early development of serotonergic neurons in the fetal rat brain

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