[Stitcher]

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Low-Level Toxicants Can Harm Brain

By Jamie Talan, Newsday, Melville, N.Y.
http://www.redorbit.com/news/health/...urce=r_health#

Feb. 6--Low levels of mercury and lead exposure can damage developing brain cells -- a finding that might help explain how these toxicants can lead to a host of mental and medical problems, a new study said.

"There is a huge problem in toxicology," said Mark Noble, a professor of biomedical genetics and neurobiology at the University of Rochester and senior author of the study in the journal PLoS Biology. "There are 80,000 to 150,000 environmental toxicants about which we know nothing. Nobody knows how to screen for them or even where to start."

His study could be a major step in identifying methods of prevention and treatment.

Noble and his colleagues conducted their work in the laboratory, where they subjected so-called glial progenitor stem cells in the brain to low levels of lead and mercury. They found that these brain cells stopped dividing. They simply shut down. The mercury levels previously were thought to be safe in humans, Noble said. "It turns out they are not."

"These levels -- 5 to 6 parts per billion -- have adverse effects on these progenitor stem cells," he said.

These cells are crucial in building the brain during infancy and beyond.

Noble said studies have shown that between 300,000 and 600,000 babies are born each year with fetal mercury levels in cord blood that are 5 to 6 parts per billion.

The researchers found that progenitor stem cells -- the brain's support cells that carry out a number of key housekeeping functions -- are extraordinarily vulnerable to low levels of toxicants. In the test tube, as many as 25 percent of the progenitor cells obtained from rats shut down when exposed to the low levels of lead or mercury.

When the researchers looked at the cellular pathways affected by these exposures, they found the toxicants were disrupting cell function by increasing oxidative stress. All the toxicants they've studied led to the same oxidative stress-producing pathway. If similar processes are taking place in the developing brain of the fetus and child, "this could certainly have adverse effects," Noble said.

Glial progenitor cells also are present in adult brains. Noble said they have no idea what effects low level environmental toxicants are having but he suspects they might be making these brain cells more vulnerable to damage and disease.

"This needs to be taken very seriously," he said. "Development is a cumulative process and the effects of even small changes in progenitor cell division and differentiation over multiple generations could have a substantial effect on an organism."

On the positive side, finding one targeted pathway provides hope for identifying a single treatment for many kinds of environmental exposures, he said. His laboratory is studying a chemical called n-acetyl-cysteine, a potent antioxidant, that works to protect this pathway and could prevent abnormal cell damage and its consequences.

[michael7733]

Carolyn,

In another thread, I think on the old forum, we discussed an entire class of chemicals that were found to fit into a mode of action known as "Oxidative Phosphorylation Inhibitors." I was particularly alarmed by how many household products contained these chemicals, and I was alarmed more so by the fact that they were deemed safe without requiring testing to verify that verdict. My hopes are that there are known safe-for-consumption enzymes, chelators or other antioxidants available to remove these toxicants from our bodies.

michael b.

[Stitcher]

Michael,

Yes, and I think about it every time I wash my hair, clean the tub without gloves, wash the dishes, put on deodorant, etc.

I know they say some chemicals are safe, but I have a hard time believing any chemical is safe.

[michael7733]

can be found here: Pesticides

I am not going to even attempt to tell you what is on these pages.


michael b.

[Stitcher]

Environmental Toxicants Like Lead, Mercury Target Stem Cells

Article Date: 07 Feb 2007 - 11:00 PST
http://www.medicalnewstoday.com/medi...&nfid=rssfeeds

Low levels of toxic substances cause critical stem cells in the central nervous system to prematurely shut down. That is the conclusion of a study published in the on-line journal PLoS Biology. This research, which is the first to identify a common molecular trigger for the effects of toxicant exposure, may give scientists new insights into damage caused by toxicant exposure and new methods of evaluating the safety of chemicals.

While scientists have long understood that certain chemicals like lead and mercury have adverse effects on the body, the precise molecular mechanism by which many of these substances cause harm remain uncertain. This makes it more difficult to concretely link individual toxic substances with specific diseases or determine - with greater confidence - whether or not a chemical is toxic. However, recent advances in molecular biology, genetics, and stem cell biology have provided scientists a new window onto the impact of toxic substances on the cellular and molecular level.

"Establishing the general principles underlying the effects of toxicant exposure on the body is one of the central challenges of toxicology research," said University of Rochester biomedical geneticist Mark Noble, Ph.D., senior author of the study. "We have discovered a previously unrecognized regulatory pathway on which chemically diverse toxicants converge and disrupt normal cell function."

Noble and his colleagues exposed a specific population of brain cells to low levels of lead, mercury, and paraquat, one of the most widely used herbicides in the world. These cells, called glial progenitors, are advanced-stage stem cells that are critical to the growth, development, and normal function of the central nervous system. The activity of cells is regulated by molecular pathways - or controlled chemical reactions - normally set off when substances bind to receptors on the cell's surface. Noble and his colleagues found that these compounds turned off specific sets of receptors and set into motion a molecular chain reaction that causes the cells to shut down and stop dividing.

"These toxicants are activating a normal cellular regulatory pathway, they are just activating it inappropriately," said Noble. "If this disruption occurs during critical developmental periods, like fetal growth or early childhood, it can have a significant impact. Development is a cumulative process, and the effects of even small changes in progenitor cell division and differentiation over multiple generations could have a substantial effect on an organism."

This study is an example of the ability of stem cell research to shed new light on many diseases and health problems that have heretofore been poorly understood by the medical community. Noble and his colleagues are pioneers in the field and have been involved in the discovery of several of the progenitor cells that are involved in building the central nervous system. The growing knowledge of the precise timing and role of these cells has enabled scientists to explore the molecular origin of these diseases, and the Rochester team's findings are part of a growing number of discoveries that indicate that certain developmental syndromes may be the result of disruption in stem cell function.

There are tens of thousands of synthetic industrial chemicals, pesticides, metals, and other substances for which toxicological information is limited or nonexistent. By identifying a molecular target that is shared by toxic substances, all with very different chemical compositions, this discovery may give scientists a method to rapidly evaluate compounds to determine whether or not they pose a potential health threat.

"One of the obstacles in the analysis of new chemicals is the difficulty in developing a system that is sensitive enough and can make predictions that are true for both individual cells and the entire organism," said Noble. "This novel pathway gives as a way to analyze a diverse array of chemicals at levels in which they would be encountered in the environment. Furthermore, by identifying a specific molecular pathway that is activated by toxic exposure, we can now begin to look at specific ways to protect cells from this disruption of signaling."

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Funding for the research came from National Institute of Environmental Health Sciences. Other investigators participating in the study were lead author Zaibo Li, M.D., Ph.D., Tiefei Dong, Ph.D., and Chris Proschel, Ph.D., all with the University of Rochester Medical Center.

Contact: Mark Michaud
University of Rochester Medical Center

[michael7733]

Now I am really concerned. Why aree these researchers just now finding this out? Several of us on the old braintalk forum discussed the mode of action of at least 4 classes of chemicals composed of many different substances, which targeted specific cellular processes. There were/are oxidaive phosphorylation inhibitors, uncouplers, those that make the cell membrane more permeable, and those that interrupt mitochondrial function by becoming out-of-place electron acceptors. All 4 of these processes, if interrupted can lead to neuron death and parkinson's disease or other neurological disorders. Professor Illingworth of the University of Leeds clearly points this out. Our own government found this out during their study of pesticides to see which ones could be used in concentrated form for biological warfare...and that was before and during WW2. There is even a database into which a chemical formula can be dumped in order to ascertain which category it fits. What disease can I get from my blood boiling?

There are tens of thousands of synthetic industrial chemicals, pesticides, metals, and other substances for which toxicological information is limited or nonexistent. By identifying a molecular target that is shared by toxic substances, all with very different chemical compositions, this discovery may give scientists a method to rapidly evaluate compounds to determine whether or not they pose a potential health threat.

michael (excuse-my-rant) b.