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Re: Methylmercury inhibits cysteine uptake in cultured primary astrocytes, but not i

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  • AndyCutler@aol.com
    I don t believe this abstract is relevant to our concerns on this list since the children were exposed long enough ago very little of the ethlymercury remains
    Message 1 of 4 , Oct 5, 2001
      I don't believe this abstract is relevant to our concerns on this list
      since the children were exposed long enough ago very little of the
      ethlymercury remains in organic form. It has mostly been converted to
      inorganic (mercuric) mercury.

      Andy

      --- In Autism-Mercury@y..., Wutsername@a... wrote:
      > Brain Res 2001 Sep 28;914(1-2):159-65
      > Methylmercury inhibits cysteine uptake in cultured primary
      astrocytes, but
      > not in neurons.
      >
      > Shanker G, Allen JW, Mutkus LA, Aschner M.
      >
      > Department of Physiology and Pharmacology, Wake Forest University
      School of
      > Medicine, Medical Center Blvd., 27157-1083, Winston-Salem, NC, USA
      >
      > The maintenance of adequate intracellular glutathione (GSH)
      concentrations is
      > dependent on the availability and transport of the rate-limiting
      substrate,
      > cysteine. A suggested mechanism of methylmercury (MeHg)
      neurotoxicity in
      > brain involves the formation of oxygen radicals, and a decrease in
      > intracellular levels of GSH. Recently, we have characterized various
      cysteine
      > transport systems (both Na(+)-dependent and -independent) in
      cerebrocortical
      > astrocytes and hippocampal neurons. The present study was carried
      out to
      > investigate the effect of MeHg on cysteine uptake in both astrocytes
      and
      > neurons, and to determine whether cysteine transport is
      differentially
      > affected in the two cell types by MeHg treatment. Sixty-minute
      pretreatment
      > with MeHg caused significant concentration-dependent inhibition in
      cysteine
      > uptake in astrocytes, but not in neurons. As most of the cysteine
      transport
      > is Na(+)-dependent (80-90% of total), additional studies focused on
      MeHg's
      > effect on the Na(+)-dependent cysteine transporters X(AG(-)) and
      ASC. An
      > additive inhibitory effect on cysteine uptake was observed in
      astrocytes
      > treated with MeHg (5 &mgr;M) plus sub-maximal inhibitory
      concentrations (0.1
      > and 0.5 mM) of threo-beta-hydroxy-aspartate (THA), a specific
      inhibitor of
      > the Na(+)-dependent transporter, X(AG(-)), compared to astrocytes
      treated
      > with MeHg (P<0.001) or THA alone (P<0.05). There was no additive
      effect of
      > MeHg and maximal inhibitory concentrations of THA (1.0 and 5.0 mM)
      on
      > astrocytic cysteine uptake inhibition. Additional studies examined
      the
      > sensitivity of the Na(+)-dependent ASC transport system to MeHg
      treatment.
      > Maximal inhibitory concentration of L-serine (10 mM) alone had a
      rather
      > modest inhibitory effect on cysteine uptake, and when applied in the
      presence
      > of MeHg there was no additive effect. These results suggest that the
      > inhibition of cysteine uptake by MeHg in astrocytes occurs through
      specific
      > inhibition of both the X(AG(-)) as well as the ASC transport system.
      >
      > PMID: 1
    • Lorilyn Teasdale
      ... From: AndyCutler@aol.com To: Autism-Mercury@yahoogroups.com Sent: Friday, October 05, 2001 2:37 PM Subject: [Autism-Mercury] Re: Methylmercury inhibits
      Message 2 of 4 , Oct 19, 2001
        ----- Original Message -----
        From: AndyCutler@...
        To: Autism-Mercury@yahoogroups.com
        Sent: Friday, October 05, 2001 2:37 PM
        Subject: [Autism-Mercury] Re: Methylmercury inhibits cysteine uptake in cultured primary astrocytes, but not i


        I don't believe this abstract is relevant to our concerns on this list
        since the children were exposed long enough ago very little of the
        ethlymercury remains in organic form. It has mostly been converted to
        inorganic (mercuric) mercury.

        Andy

        --- In Autism-Mercury@y..., Wutsername@a... wrote:
        > Brain Res 2001 Sep 28;914(1-2):159-65
        > Methylmercury inhibits cysteine uptake in cultured primary
        astrocytes, but
        > not in neurons.
        >
        I have not seen such a promising piece of information as this article, which R posted, in all the emails I have read on this or any list. This could be the key to a model for Autism etiology, in my opinion. To suggest it is not relevent is to suggest that the answer to the cause of this disese is known a priori.

        Let me explain. Many of us parents report responses to Thimerisol containing injections within hours, days or weeks. This is just too short a time to be a result to inorganic mercury insult. The reduction of org Hg takes weeks to months. I have long suspected that there was a concurrent interaction with ethyl Hg / Hg++ and the brain. Further, a differential response by the various cells within the brain fits in perfectly with my model for development of the disease. Asrocytes, when grown in vitro with neurons, spur on neurons to generate 20 times more dendrites along their axons. Since language development and other behaviors associated with Autism are late onset, the growth and movement of dendrites in making and breaking contacts to adjacent neurons is fundamental to this process. If, when the time comes for this to happen, the support cells, the astrocytes (and Perjinke cells?) are damaged, then this could provide a good model for the onset of Autism.

        If cysteine uptake is blocked (or there are other differential impairments to these cells), an oxidative stress could subsequently damage or kill these cells. The organic Hg camps out in cells as it slowly converts over to Hg++. One can reason that over time, the anti-oxidant chain is inhibited for this long period, as the org Hg is slowly converted. The astrocytes would be open to chemical or radiation assualt if the inhibition of Cysteine uptake is shut down. No astrocytes, no language development? Unless the kid takes Secretin, which appears to supercharge the neurotransmitters in the amygdala and temporarily overcomes the lack of numerous dedritic connections.

        I believe that this serendipitous piece of information is germaine to this list. My theory may be incorrect. If correct, then it could offer hope to the +10 year old autistic, whom only a small fraction appear to show any improvement with chelation. Stem cell derived astrocytes, combined with neural growth factor after full chelation regimens could be the key to their full recovery. I sincerely hope that this list remains open to and actually encourages off-the-wall bits of information, even if marginally related to the mercury/autism connection.



        [Non-text portions of this message have been removed]
      • Lorilyn Teasdale
        I think I should point out that my husband, Ken, has been posting on this topic under my name. He is a scientist, I am not. Lorilyn [Non-text portions of this
        Message 3 of 4 , Oct 19, 2001
          I think I should point out that my husband, Ken, has been posting on this topic under my name. He is a scientist, I am not.
          Lorilyn



          [Non-text portions of this message have been removed]
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