New study shows mechanism- even very low level of Mercury causes brain inflammation, autism

[Guest guest]

brand new study in the Journal of Neuroinflammation. Please share widely.

<http://www.jneuroinflammation.com/>

<http://www.ncbi.nlm.nih.gov/pubmed/20222982>

Mercury induces inflammatory mediator release from

human mast cell " We, therefore, investigated whether HgCl2 could stimulate human

mast cells, an action that could

be enhanced in subjects who already have an atopic background. "

.... " We then investigated whether HgCl2 could stimulate release of

proinflammatory mediators from

mast cells. "

Discussion

This is the first report to our knowledge showing that inorganic mercury in

concentrations as low

as 0.1 μM can induce VEGF and IL-6 release from human cultured mast cells. We

also report

for the first time that mercury has a significant synergistic effect with SP

(0.1 μM) on VEGF

release; this amount of VEGF release is higher than what has previously been

reported for

hCBMCs [19]. One paper has reported that HgCl2 can induce release of histamine

from primary

lung and human leukemic mast cells (HMC-1 cells), but only at toxic levels of

0.33 mM [20].

Here we show that HgCl2 induces β-hexosaminidase release, but only at a

concentration of 10

μM. Mercury (10 μM) has previously been shown to induce release of

β-hexosaminidase, IL-4

and TNF-α from a murine mast cell line and from mouse bone marrow-derived

cultured mast

cells; the secretion of cytokines mediated by HgCl2 is additive to that which

follows

FcepsilonRI-induced mast cell activation [11]. In contrast, HgCl2 does not have

an effect on its

own on release of histamine and IL-4 from human basophil, but only enhances

allergic release at

concentrations of 1 and 10 μM [12]. This is also true for IL-4 release from rat

mast cells [21].

Clinical symptoms of mercury poisoning may be expected at blood levels of 1 μM

[12].

However, brain mast cells may react to lower mercury concentrations, especially

in vulnerable

patient subpopulations.

Mast cells, by virtue of their location in the skin, respiratory tract, and

gastrointestinal system are

potential targets for environmental agents with immunotoxic effects [22]. Mast

cells are critical

not only for allergic reactions, but also important in both innate and acquired

immunity [23], as

well as in inflammation [24]. In view of the fact that a subgroup of ASD

patients have allergy

symptoms that do not appear to be triggered by IgE, it is noteworthy that mast

cells can be

stimulated by non-allergic triggers originating in the gut or the brain [24],

especially

neuropeptides such as SP [25] and neurotensin (NT) [26]. Once activated, mast

cells secrete

numerous vasoactive, neurosensitizing and proinflammatory molecules that are

relevant to ASD;

these include histamine, proteases, VEGF, prostaglandin D2, as well as cytokines

such as IL-6

[24]. In particular, mast cells can secrete VEGF [27, 28], an isoform of which

is vasodilatory

[29] and is over expressed in delayed hypersensitivity reactions [30]. In fact,

mast cells can

release VEGF [31], IL-6 [32] and other mediators “selectively†without

degranulation [33].

Such mediators could disrupt the gut-blood and blood-brain barriers (BBB)

permitting brain

inflammation [34]. It is important to note that mercury can cross the BBB

through a transport

mechanism that can lead to significant brain concentrations, and that can

persist for prolonged

periods of time [2, 35]. Activated brain mast cells can disrupt the BBB [36, 37]

and further

increase brain mercury levels.

The mechanisms of heavy metal neurotoxicity are not fully understood. Mercury

increases

cytosolic calcium levels in PC12 cells [38], and thimerosal does so in thymus

lymphocytes [39].

Mercury may also increase cellular oxidative stress since neurons are highly

susceptible to

reactive oxygen species (ROS) and neuronal mitochondria are especially

vulnerable to oxidative

damage [40]. In fact, the primary dietary source of neurotoxic mercury compounds

is via the

ingestion of methylmercury from fish, which has been previously linked to

neurological damage

[41].

Mercury’s activation of mast cell inflammatory mediator release may enhance

allergic reactions

in atopic individuals and exacerbate IgE-dependent diseases [12]. Allergic

symptomatology is

often present in ASD patients [34], and a survey of children with ASD in Italy

reported that the

strongest association was with a history of allergies [42]. Moreover, a recent

study reported

increased atopic diseases, as well as elevated serum IgE and eosinophils in

Asperger patients

[43]. In a National Survey of Children’s Health, parents of autistic children

reported symptoms

of allergies more often than other children, with food allergies showing the

greatest difference

[44]. A case series study also reported higher rate of food allergies in ASD

children [45]. In one

study, 30% of autistic children (n=30) had a history of atopy as compared to

2.5% of agematched

“neurologic controls†(n=30), but there was no difference in serum IgE or in

skin prick

tests to 12 common antigens [46], implicating triggers other than IgE. In

another study, ASD

patients did not have increased incidence of allergic asthma or allergic

dermatitis [42], but this

study included only ASD patients that were positive to RAST/skin testing.

Finally, a preliminary

report indicated that the prevalence of ASD may be 10-fold higher [47] than the

general

population (1/100 children) in mastocytosis patients [48], characterized by

increased number of

hyperactive mast cells in many tissues, with symptoms that include allergies,

food intolerances

and “brain fog†[49, 50].

Some epidemiological studies have failed to find a significant relationship

between mercury

exposure from vaccines and autism [3-7]. Nevertheless, 87% of children included

in the US

Vaccine Adverse Event Reporting System (VAERS) have ASD [8]. Moreover, a paper

based on

computerized medical records in the Vaccine Safety Datalink concluded there was

“significantly

increased rate ratios for ASD with mercury exposure from Thimerosal-containing

vaccines†[9].

Also, there are a series of epidemiological studies conducted in the USA that

have found

significant associations between environmental sources of mercury exposure and

ASDs [51]. In

addition, patients with severe ASD have evidence of significantly increased

urinary porphyrins

consistent with mercury intoxication [52-55]. Mercury toxicity may also affect

critical

methylation pathways in vulnerable cells [56].

ASD are a group of pervasive developmental disorders that include autistic

disorder, Asperger’s

disorder, and atypical autism - also known as pervasive developmental

disorder-not otherwise

specified (PDD-NOS). These are neurodevelopmental disorders diagnosed in early

childhood

[57]. They are characterized by various degrees of dysfunctional communication

and social

skills, repetitive and stereotypic behaviors, as well as attention, cognitive,

learning and sensory

defects [57, 58]. ASD cases have increased more than 10-fold during the last

decade to a

prevalence of 1/100 children [44, 57, 59]. However, there is no known distinct

pathogenesis,

there are no biomarkers, and there is no effective treatment [60].

ASD may result from a combination of genetic/biochemical susceptibility and

epigenetic

exposure to environmental factors, including reduced ability to excrete mercury

and/or exposure

to mercury at critical developmental periods [2, 56]. A number of papers have

suggested that

ASD may be associated with immune dysfunction [61], while a recent review made

the case that

ASD may be a neuroimmune disorder involving mast cell activation [34].

Conclusions

The results of the present study support the biological plausibility of how

mercury could

contribute to ASD pathogenesis by inducing VEGF and IL-6 release from mast

cells, and as a

result disrupt the BBB and thus permit brain inflammation. Further studies

should investigate the

effect of mercury and thimerosal alone or together with allergic and non-immune

triggers.

Study Attached. 

blessings,

Liora Pearlman , ModeratorMom

" Once our eyes are opened, we can't pretend we don't know what to do.   G-d,

who weighs our hearts and keeps our souls, knows that we know and holds us

responsible to act. "  Proverbs (Mishlei) 24:12 

" Leave your drugs in the chemist's pot if you can heal the patient with food "

HIPPOCRATES The Father of Medicine