Re: Fw: [Autism-Mercury] CNS-glutathione astrocytes mercury thimerosal

[Guest guest]

Yes, I just joined this afternoon. I understand somewhat of what is going

on, but what I am trying to find out is how do you know if your autistic

child has mercury poisoning. Jen has had so many tests I do not know what

end is sometimes. She did have a test that I had to cut some of hair and

send to a lab, but I never heard again about the results from the doctor. I

think the test pertained to Yeast, but maybe it was something other than

yeast.

I have friend that lives near me who has an autistic boy with mercury. She

seem very confused. She is doing everything the doctor is tell her to do.

She thinks the doctor was talking about something call " T-factor " . In the

last few months she has given me three different descriptions of the

treatment her son is going to receive.

Take care and God Bless,

Beverly Weakley

Mom of Jen

[Autism-Mercury] CNS-glutathione astrocytes mercury thimerosal

> >

> >

> > >Glutathione's role in mercury toxicity within the CNS is complex. A

> > >1994 study by Aschner & colleagues focused upon intracellular

> > >glutathione (GSH) in regard to amino acid release from astrocytes (1).

> > >

> > >The topic of peripheral and CNS GSH-levels at the time of ethylmercury

> > >(eHg) injections differs from the issue of chelation strategies years

> > >subsequent to thimerosal exposure. This post focuses upon GSH-levels

> > >within the CNS as they might have influenced a child's susceptibility

> > >to eHg neurotoxicity and neurobehavioral sequelae at the time eHg was

> > >injected.

> > >

> > >A ramification of the Aschner et al study is as follows:

> > > If an abundance of excitatory neurotransmitters leads to

> > >epileptiform activity in the hours, days, and weeks subsequent to an

> > >infant's or toddler's eHg injection, then subsequent epileptiform

> > >activity would be more likely and the level of neuronal damage greater

> > >(Tuunanen et al, series of studies). Aschner et al report that

> > >astrocytic mercury leads to increased release of excitatory

> > >neurotransmitters and that this release is enhanced if GSH is low.

> > >

> > >I realize that physiological processes involving GSH are complex.

> > >Nonetheless, when seeking to understand why some infants and toddlers

> > >are more susceptible to eHg neurotoxicity from thimerosal injections,

> > >any and all conditions whereby GSH is lowered would seem to increase

> > >the likelihood of neurologic sequelae.

> > >

> > >A previous post offered citations supporting a role for peripheral GSH

> > >in protecting against organic mercury. That post may be retrieved by

> > >using egroups jump-to function (post 4398 in autism-mercury) entitled:

> > > " peripheral glutathione and elimination of organic mercury " .

> > >Here are some Aschner et al quotes about CNS glutathione:

> > >

> > >1. " Astrocytes in the mammalian CNS are known targets of Hg exposure.

> > >Recent in vivo and in vitro studies suggest that the neurotoxicity

> > >of mercry (Hg) species may be associated with astrocytic dysfunction

> > >leading to a failure of astrocytes to adequately control the

> > >composition of the extracellular environment. "

> > >2. " Astrocytes release excitatory amino acids (EAAs) in response to a

> > >variety of stimuli including neurotransmitters. and exposure to

> > >xenobiotics [such as organic mercury]. "

> > >3. " We have recently shown that two sulfhydryl-(SH-)protecting agents:

> > >a cell membrane non-penetrating compound, reduced glutathione (GSH),

> > >and the membrane permeable dithiothreitol (DTT), inhibit the direct

> > >stimulatory action. of MC [mercuric cloride] and MeHg on the effleus

> > >of. D-aspartate. "

> > >4. " The results presented herein imply that astrocytic GSH levels can

> > >modify both MC- and MeHg-induced. D-aspartate and .D-taurine release

> > >by astrocytes. "

> > >5. When GSH levels are reduced., MC- and MeHg-induced release of D-

> > >aspartate and D-taurine is enhanced. "

> > >6. " Treating the cells with. [a lab chemical] reported to supplement

> > >GSH resyhthesis by delivering cysteine to cells, and shown here to

> > >increase GSH in primary astrocyte cultures, attenuated the MC- and

> > >MeHg-induced amino acid release. "

> > >7. " Several mechanisms for the protective role of GSH on MC- and MeHg-

> > >induced amino acid release from astrocytes are proposed:

> > >complexation of MC or MgHg with GSH and subsequent transport by GSH

> > >and/or GSH-S-conjugate carriers can provide for a transport vehicle,

> > >leading to reduced toxicity by virtue of reduced intracellular

> > >concentrations of these mercurials. "

> > >8. " Support for this mechanism is also derived from studies on MeHg

> > >efflux from liver to bile, a transport system that is extensively

> > >characterized. MeHg secretion from liver to bile closely parallels

> > >the secretion of GSH., and inhibitors that block GSH secretion. also

> > >block MeHg secretion. "

> > >9. " Given the high concentration of GSH in astrocytes, it is reasonable

> > >to assume the MeHg will bind to GSH, affording a vehicle for

> > >transport out of astrocytes. "

> > >10. " A second protective mechanism against MC- and MeHg-induced

> > >toxicity may be related to increased -SH " buffering' capacity in

> > >`GHS-enriched' cells, limiting the association of mercurials with

> > >essential -SH sites on the D-aspartate and D-taurine transporters. "

> > >11. " A third mechanism for the protective effects of increased GSH on

> > >amino acid release invokes its antioxidant properties. also by

> > >protecting and regenerating vitamin E, which in turn protects lipid

> > >bilayers from peroxidation. "

> > >12. " In addition to the pathophysiologic implications of the

> > >relationship between mercury and GSH, the distribution of GSH within

> > >the CNS may explain the propensity of astrocytes to accumulate this

> > >heavy metal. The importance of GSH to cell metabolism is evidenced

> > >by its presence in virtually all cells and its relatively rapid

> > >intracellular turnover. Interestingly, however, histochemical

> > >evidence suggests that little GSH is present in neurons. wherease

> > >high GSH [levels] are found in astrocytes. "

> > >

> > >Conclusion: The importance of adequent GSH at in the hours, days, and

> > >weeks subsequent to physician-injected ethylmercury seems well

> > >established -- for both peripheral and CNS glutathione. A child with

> > >low GSH -- whether due to genetic or non-genetic factors or both --

> > >would seem at increased risk for thimerosal-induced neurotoxicity and

> > >neurobehavioral sequelae. Aschner et al conclude: " In summary, the

> > >current data emphasize both the sensitivity of astrocytes to mercury

> > >and the importance of GSH in modulating [and lowering] mercury-induced

> > >[excitatory] amino acid release. "

> > >

> > >

> > >

> > >Reference:

> > >

> > >1. The following article was published by Elsevier and thus may be free

> > >and available as a pdf via http://www.neuroscion.com

> > >

> > >Brain Res 1994 Nov 21;664(1-2):133-40

> > >Intracellular glutathione (GSH) levels modulate mercuric chloride (MC)-

> > >and

> > >methylmercuric chloride (MeHgCl)-induced amino acid release from

> > >neonatal rat

> > >primary astrocytes cultures.

> > >Aschner M, Mullaney KJ, Wagoner D, Lash LH, Kimelberg HK

> > >Department of Pharmacology and Toxicology, Albany Medical College, NY.

> > >

> > >Mercuric chloride (MC) and methylmercury (MeHg) were found to increase

> > >amino

> > >acid release from astrocytes. This suggests interaction with sulfhydryl

> > >(-SH)

> > >groups which are controlled by glutathione [GSH] levels. In the present

> > >study,

> > >we evaluated the effects of alterations in intracellular glutathione

> > >concentrations [GSH]i on the outcome of MC and MeHg treatment. [GSH]i

> > >were

> > >increased in a time-dependent fashion by incubating the astrocytes with

> > >1 mM

> > >L-2-oxothiazolidine-4-carboxylic acid (OTC), a cysteine precursor. OTC

> > >attenuated the release of [2,3-3H]D-aspartic acid from astrocytes

> > >exposed to MC-

> > >(5 microM) and MeHg-(10 microM). MeHg-induced [3H]D-taurine release was

> > >also

> > >reduced by pretreatment of astrocytes with OTC. Treatment with BSO (50

> > >microM)

> > >decreased [GSH]i in astrocytes, and increased [2,3-3H]D-aspartate

> > >release from

> > >MC- and MeHg-treated astrocytes, and [3H]D-taurine release from

> > >MeHg-treated

> > >cells. Neither OTC nor BSO when added to cultures in the absence of MC

> > >or MeHg

> > >had an effect on amino acid release by astrocytes. The current study

> > >underscores

> > >both the sensitivity of astrocytes to mercurials in terms of amino acid

> > >release

> > >and the relationship of these effects of astrocytic [GSH]i.

> > >

> > >2. Aschner and colleagues have enacted many studies about organic

> > >mercury and

> > >its effects upon astrocytes:

> > >

> > >1: Aschner M, Yao CP, JW, Tan KH. Methylmercury alters glutamate

> > >transport

> > >in astrocytes.

> > >Neurochem Int. 2000 Aug-Sep;37(2-3):199-206.

> > >2: Yao CP, JW, Aschner M.Metallothioneins attenuate

> > >methylmercury-induced

> > >neurotoxicity in cultured astrocytes and astrocytoma cells.

> > >Ann N Y Acad Sci. 1999;890:223-6.

> > >3: Yao CP, JW, Mutkus LA, Xu SB, Tan KH, Aschner M.Foreign

> > >metallothionein-I expression by transient transfection in MT-I and

MT-II

> > >null

> > >astrocytes confers increased protection against acute methylmercury

> > >cytotoxicity. Brain Res. 2000 Feb 7;855(1):32-8.

> > >4: Aschner M.Immune and inflammatory responses in the CNS: modulation

by

> > >

> > >astrocytes. Toxicol Lett. 1998 Dec 28;102-103:283-7. Review.

> > >5: Aschner M, Vitarella D, JW, Conklin DR, Cowan

> > >KS.Methylmercury-induced

> > >inhibition of regulatory volume decrease in astrocytes:

characterization

> > >of

> > >osmoregulator efflux and its reversal by amiloride.

> > >Brain Res. 1998 Nov 16;811(1-2):133-42.

> > >6: Aschner M.Astrocytes as mediators of immune and inflammatory

> > >responses in the

> > >CNS. Neurotoxicology. 1998 Apr;19(2):269-81. Review.

> > >7: Aschner M.Astrocytes as modulators of mercury-induced neurotoxicity.

> > >Neurotoxicology. 1996 Fall-Winter;17(3-4):663-9. Review.

> > >8: Aschner M.Methylmercury in astrocytes--what possible significance?

> > >Neurotoxicology. 1996 Spring;17(1):93-106. Review.

> > >9: Aschner M, Mullaney KJ, Fehm MN, Wagoner DE Jr, Vitarella

> > >D.Astrocytes as

> > >potential modulators of mercuric chloride neurotoxicity.

> > >Cell Mol Neurobiol. 1994 Dec;14(6):637-52.

> > >10: Aschner M, Mullaney KJ, Wagoner D, Lash LH, Kimelberg

> > >HK.Intracellular

> > >glutathione (GSH) levels modulate mercuric chloride (MC)- and

> > >methylmercuric

> > >chloride (MeHgCl)-induced amino acid release from neonatal rat primary

> > >astrocytes cultures. Brain Res. 1994 Nov 21;664(1-2):133-40.

> > >11: Dave V, Mullaney KJ, Goderie S, Kimelberg HK, Aschner M.Astrocytes

> > >as

> > >mediators of methylmercury neurotoxicity: effects on D-aspartate and

> > >serotonin

> > >uptake. Dev Neurosci. 1994;16(3-4):222-31.

> > >12: Dave V, Vitarella D, Aschner JL, Fletcher P, Kimelberg HK, Aschner

> > >M.Lead

> > >increases inositol 1,4,5-trisphosphate levels but does not interfere

> > >with

> > >calcium transients in primary rat astrocytes.

> > >Brain Res. 1993 Jul 30;618(1):9-18.

> > >13: Aschner M, LoPachin RM Jr.Astrocytes: targets and mediators of

> > >chemical-induced CNS injury.

> > >J Toxicol Environ Health. 1993 Mar;38(3):329-42. Review.

> > >14: Aschner M, Gannon M, Kimelberg HK.Manganese uptake and efflux in

> > >cultured

> > >rat astrocytes.

> > >J Neurochem. 1992 Feb;58(2):730-5.

> > >15: Aschner M, Chen R, Kimelberg HK.Effects of mercury and lead on

> > >rubidium

> > >uptake and efflux in cultured rat astrocytes.

> > >Brain Res Bull. 1991 Apr;26(4):639-42.

> > >16: Aschner M, Kimelberg HK.The use of astrocytes in culture as model

> > >systems

> > >for evaluating neurotoxic-induced-injury.

> > >Neurotoxicology. 1991 Fall;12(3):505-17. Review.

> > >

> > >

> > >

> > >

> > >

> > >

> > >

> > >

> >

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