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Lead exposure and schizophrenia


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#1 DocM

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Posted 03 June 2013 - 10:01

http://medicalxpress...izophrenia.html

Lead acts to trigger schizophrenia

Mice engineered with a human gene for schizophrenia and exposed to lead during early life exhibited behaviors and structural changes in their brains consistent with schizophrenia. Scientists at Columbia University's Mailman School of Public Health and the Johns Hopkins University School of Medicine say their findings suggest a synergistic effect between lead exposure and a genetic risk factor, and open an avenue to better understanding the complex gene-environment interactions that put people at risk for schizophrenia and other mental disorders.

Results appear online in Schizophrenia Bulletin.

Going back to 2004, work by scientists at the Mailman School suggested a connection between prenatal lead exposure in humans and increased risk for schizophrenia later in life. But a big question remained: How could lead trigger the disease? Based on his own research, Tomas R. Guilarte, PhD, senior author of the new study, believed the answer was in the direct inhibitory effect of lead on the N-methyl-D-aspartate receptor (NMDAR), a synaptic connection point important to brain development, learning, and memory. His research in rodents found that exposure to lead blunted the function of the NMDAR. The glutamate hypothesis of schizophrenia postulates that a deficit in glutamate neurotransmission and specifically hypoactivity of the NMDAR can explain a significant portion of the dysfunction in schizophrenia.

In the new study, Dr. Guilarte, professor and chair of the department of Environmental Health Sciences at the Mailman School, and his co-investigators focused on mice engineered to carry the mutant form of Disrupted-in-Schizophrenia-1 (DISC1), a gene that is a risk factor for the disease in humans. Beginning before birth, half of the mutant DISC1 mice were fed a diet with lead, and half were given a normal diet. A second group of normal mice not expressing the mutant DISC1 gene were also split into the two feeding groups. All mice were put through a battery of behavioral tests and their brains were examined using MRI.

Mutant mice exposed to lead and given a psychostimulant exhibited elevated levels of hyperactivity and were less able to suppress a startle in response to a loud noise after being given an acoustic warning. Their brains also had markedly larger lateral ventricles—empty spaces containing cerebrospinal fluid—compared with other mice. These results mirror what is known about schizophrenia in humans.

While the role of genes in schizophrenia and mental disorders is well established, the effect of toxic chemicals in the environment is only just beginning to emerge. The study's results focus on schizophrenia, but implications could be broader.

"We're just scratching the surface," says Dr. Guilarte. "We used lead in this study, but there are other environmental toxins that disrupt the function of the NMDAR." One of these is a family of chemicals in air pollution called polycyclic aromatic hydrocarbons or PAHs. "Similarly, any number of genes could be in play," adds Dr. Guilarte, noting that DISC1 is among many implicated in schizophrenia.

Future research may reveal to what extent schizophrenia is determined by environmental versus genetic factors or their interactions, and what other mental problems might be in the mix. One ongoing study by Dr. Guilarte is looking at whether lead exposure alone can contribute to deficits of one specialized type of neuron called parvalbumin-positive GABAergic interneuron that is known to be affected in the brain of schizophrenia patients. Scientists are also interested to establish the critical window for exposure—whether in utero or postnatal, or both.

"The animal model provides a way forward to answer important questions about the physiological processes underlying schizophrenia," says Dr. Guilarte.

Provided by Columbia University's Mailman School of Public Health




#2 +zhiVago

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Posted 03 June 2013 - 11:13

Lead poisoning

Routes of exposure to lead include contaminated air, water, soil, food, and consumer products. Occupational exposure is a common cause of lead poisoning in adults. According to estimates made by the National Institute of Occupational Safety and Health (NIOSH), more than 3 million workers in the

United States are potentially exposed to lead in the workplace.[1] One of the largest threats to children is lead paint that exists in many homes, especially older ones; thus children in older housing with chipping paint or lead dust from moveable window frames with lead paint are at greater risk. Prevention of lead exposure can range from individual efforts (e.g. removing lead-containing items such as piping or blinds from the home) to nationwide policies (e.g. laws that ban lead in products, reduce allowable levels in water or soil, or provide for cleanup and mitigation of contaminated soil, etc.).

Elevated lead in the body can be detected by the presence of changes in blood cells visible with a microscope and dense lines in the bones of children seen on X-ray. However, the main tool for diagnosis is measurement of the blood lead level. When blood lead levels are recorded, the results indicate how much lead is circulating within the blood stream, not the amount being stored in the body.[2] There are two units for reporting blood lead level, either micrograms per deciliter (µg/dl), or micrograms per 100 grams (µg/100 g) of whole blood, which are numerically equivalent. The Centers for Disease Control (US) has set the standard elevated blood lead level for adults to be 10 (µg/dl) of the whole blood. For children however, the number is set much lower at 5 (µg/dl) of blood as of 2012[3] down from a previous 10 (µg/dl).[4] Children are especially prone to the health effects of lead and as a result, blood lead levels must be set lower and closely monitored if contamination is possible.[2] The major treatments are removal of the source of lead and chelation therapy (administration of agents that bind lead so it can be excreted).

Humans have been mining and using this heavy metal for thousands of years, poisoning themselves in the process. Although lead poisoning is one of the oldest known work and environmental hazards, the modern understanding of the small amount of lead necessary to cause harm did not come about until the latter half of the 20th century. No safe threshold for lead exposure has been discovered—that is, there is no known amount of lead that is too small to cause the body harm.



#3 Lant

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Posted 03 June 2013 - 20:42

Got to love Tetraethyl Lead, I mean apart from CFCs how much more damaging a chemical could you invent and then put loads of it in the atmosphere?

And were still making it...

#4 Growled

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Posted 04 June 2013 - 20:04

Too bad we didn't know the bad effects of lead years ago.

#5 Draconian Guppy

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Posted 04 June 2013 - 20:06

Too bad we didn't know the bad effects of lead years ago.


:laugh:

#6 OP DocM

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Posted 04 June 2013 - 20:15

Too bad we didn't know the bad effects of lead years ago.


:)

Seriously, the Greek physician Pedanius Dioscorides wrote of lead's deleterious effects on the human mind in the 1st century, then Germany's Eberhard Gockel noted other toxic effects in the 17th century. They and others have largely been ignored in much of the world.

#7 Growled

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Posted 04 June 2013 - 20:17

:)

Seriously, the Greek physician Pedanius Dioscorides wrote of lead's deleterious effects on the human mind in the 1st century, then Germany's Eberhard Gockel noted other toxic effects in the 17th century. They and others have largely been ignored in much of the world.


Oh, I know Doc. I was being sarcastic again.

#8 arachnoid

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Posted 04 June 2013 - 20:19

Yea ,had Nero ate off plastic plates Rome would never have burnt :rolleyes: :laugh: