Methylmercury Causes Blood-Brain Barrier Damage in Rats via Upregulation of Vascular Endothelial Growth Factor Expression

Fujimura, Masatake; Koyama, Misaki; Kanazawa, Masato; Usuki, Fusako; Nishizawa, Masatoyo; Shimohata, Takayoshi

doi:10.1371/journal.pone.0170623

Cited by 48 publications

(25 citation statements)

References 26 publications

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“…Other reporters [36] explained that the way of action of Me Hg induced neurotoxicity mediated through damaging of Blood-Brain Barrier (BBB) and alteration of calcium homeostasis and glutamate homoeostasis; moreover it helps in induction of apoptosis or necrosis.…”

Section: Discussionmentioning

confidence: 99%

Effect of Methyl Mercury on the Cerebellar Cortex of Rats and the Possible Neuroprotective Role of Mesenchymal Stem Cells Conditioned Medium. Histological and Immunohistochemical Study

El-Azab¹,

El-Mahalaway²,

Sabry³

2018

J Stem Cell Res Ther

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Background: Methyl mercury (Me Hg) is an environmental toxin associated with many serious neurological disorders. Conditioned Medium (CM) derived from Mesenchymal Stem Cells (MSCs) is a novel promising approach for the treatment of nervous system damage and various diseases. Objective: The aim of this research is to assess the consequence of Me Hg on the rats' cerebellar cortex and the potential neuroprotective effect of MSCs-CM. Materials and methods: Forty adult male albino rats were divided into four groups: Group I: control rats; Group II: Me Hg chloride treated rats; Group III: Me Hg chloride and DMEM treated rats; Group IV: CM treated rats after injection with Me Hg chloride. Cerebellar specimens were taken and handled for histological and immunohistochemical techniques. Morphometrical studies and statistical analysis were performed. Results: Groups II and III showed various changes such as neuronal degeneration and apoptosis. The mean number of Purkinje cells was significantly decreased(P<0.01), while Glial Fibrillary Acidic Protein (GFAP) immunostaining was significantly increased (P<0.01) in the neuroglial cells. Ultrastructural examination showed thinning and apparent decrease in the number of myelinated nerve axons. Shrunken Purkinje cells were observed with irregular nuclei, heterogenous cytoplasm, and disrupted mitochondria. Group IV showed improvement of the histological and electron microscopic changes defined in groups II and III. Conclusion: Me Hg exposure led to degenerative changes on cerebellar cortex. MSCs-CM is a very promising approach and has neuroprotective effects.

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Section: Discussionmentioning

confidence: 99%

Effect of Methyl Mercury on the Cerebellar Cortex of Rats and the Possible Neuroprotective Role of Mesenchymal Stem Cells Conditioned Medium. Histological and Immunohistochemical Study

El-Azab¹,

El-Mahalaway²,

Sabry³

2018

J Stem Cell Res Ther

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“…Additionally, mercury intoxication increases vascular endothelial growth factor expression, increasing BBB permeability (Takahashi et al 2017;Takahashi and Shimohata 2019). Actually, the etiology of brain mercury toxicity is the impairment of the BBB (Steinwall and Klatzo 1966;Steinwall and Olsson 1969;Takahashi and Shimohata 2019).…”

Section: Brain Mercury Accumulationmentioning

confidence: 99%

First record on mercury accumulation in mice brain living in active volcanic environments: a cytochemical approach

Navarro‐Sempere

Segovia

Rodrigues

et al. 2020

Environ Geochem Health

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The health effects of mercury vapor exposure on the brain in volcanic areas have not been previously addressed in the literature. However, 10% of the worldwide population inhabits in the vicinity of an active volcano, which are natural sources of elemental mercury emission. To evaluate the presence of mercury compounds in the brain after chronic exposure to volcanogenic mercury vapor, a histochemical study, using autometallographic silver, was carried out to compare the brain of mice chronically exposed to an active volcanic environment (Furnas village, Azores, Portugal) with those not exposed (Rabo de Peixe village, Azores, Portugal). Results demonstrated several mercury deposits in blood vessels, white matter and some cells of the hippocampus in the brain of chronically exposed mice. Our results highlight that chronic exposure to an active volcanic environment results in brain mercury accumulation, raising an alert regarding potential human health risks. These findings support the hypothesis that mercury exposure can be a risk factor in causing neurodegenerative diseases in the inhabitants of volcanically active areas.

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“…Studies have found mercury causes blood-brain barrier damage [89]. Once damaged, toxins can enter the brain with greater ease.…”

Section: Discussionmentioning

confidence: 99%

A Hypothesis and Evidence That Mercury May be an Etiological Factor in Alzheimer’s Disease

Siblerud

Mutter

Moore

et al. 2019

IJERPH

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Mercury is one of the most toxic elements and causes a multitude of health problems. It is ten times more toxic to neurons than lead. This study was created to determine if mercury could be causing Alzheimer’s disease (AD) by cross referencing the effects of mercury with 70 factors associated with AD. The results found that all these factors could be attributed to mercury. The hallmark changes in AD include plaques, beta amyloid protein, neurofibrillary tangles, phosphorylated tau protein, and memory loss—all changes that can be caused by mercury. Neurotransmitters such as acetylcholine, serotonin, dopamine, glutamate, and norepinephrine are inhibited in patients with Alzheimer’s disease, with the same inhibition occurring in mercury toxicity. Enzyme dysfunction in patients with Alzheimer’s disease include BACE 1, gamma secretase, cyclooxygenase-2, cytochrome-c-oxidase, protein kinases, monoamine oxidase, nitric oxide synthetase, acetyl choline transferase, and caspases, all which can be explained by mercury toxicity. Immune and inflammatory responses seen in patients with Alzheimer’s disease also occur when cells are exposed to mercury, including complement activation, cytokine expression, production of glial fibrillary acid protein antibodies and interleukin-1, transforming growth factor, beta 2 microglobulins, and phosphodiesterase 4 stimulation. Genetic factors in patients with Alzheimer’s disease are also associated with mercury. Apolipoprotein E 4 allele increases the toxicity of mercury. Mercury can inhibit DNA synthesis in the hippocampus, and has been associated with genetic mutations of presenilin 1 and 2, found in AD. The abnormalities of minerals and vitamins, specifically aluminum, calcium, copper, iron, magnesium, selenium, zinc, and vitamins B1, B12, E, and C, that occur in patients with Alzheimer’s disease, also occur in mercury toxicity. Aluminum has been found to increase mercury’s toxicity. Likewise, similar biochemical factors in AD are affected by mercury, including changes in blood levels of homocysteine, arachidonic acid, DHEA sulfate, glutathione, hydrogen peroxide, glycosamine glycans, acetyl-L carnitine, melatonin, and HDL. Other factors seen in Alzheimer’s disease, such as increased platelet activation, poor odor identification, hypertension, depression, increased incidences of herpes virus and chlamydia infections, also occur in mercury exposure. In addition, patients diagnosed with Alzheimer’s disease exhibit higher levels of brain mercury, blood mercury, and tissue mercury in some studies. The greatest exogenous sources of brain mercury come from dental amalgams. Conclusion: This review of the literature strongly suggests that mercury can be a cause of Alzheimer’s Disease.

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Methylmercury Causes Blood-Brain Barrier Damage in Rats via Upregulation of Vascular Endothelial Growth Factor Expression

Cited by 48 publications

References 26 publications

Effect of Methyl Mercury on the Cerebellar Cortex of Rats and the Possible Neuroprotective Role of Mesenchymal Stem Cells Conditioned Medium. Histological and Immunohistochemical Study

Effect of Methyl Mercury on the Cerebellar Cortex of Rats and the Possible Neuroprotective Role of Mesenchymal Stem Cells Conditioned Medium. Histological and Immunohistochemical Study

First record on mercury accumulation in mice brain living in active volcanic environments: a cytochemical approach

A Hypothesis and Evidence That Mercury May be an Etiological Factor in Alzheimer’s Disease

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