Sunday, March 17, 2024

Toxins That Cause Parkinson’s

One Of The First Studies To Look At Human Cells

Is Parkinson’s disease related to pesticide use? | DW Documentary

The researchers used stem cells from patients with Parkinsons disease who had a mutation in the gene responsible for encoding the -synuclein protein.

At least 30 alterations in this gene have been associated with Parkinsons, and -synuclein protein clumps are a well-documented, albeit poorly understood, hallmark of the disease.

For the new research, the scientists also worked with normal embryonic cells that they modified using genetic editing to replicate the -synuclein genetic mutation.

Prof. Ryan explains why using human cells makes this study particularly valuable. Until now, he says, the link between pesticides and Parkinsons disease was based primarily on animal studies as well as epidemiological research that demonstrated an increased risk among farmers and others exposed to agricultural chemicals.

We are one of the first to investigate what is happening inside human cells, explains Prof. Ryan.

Stem cells are undifferentiated cells that go on to individualize into specific types of cells. Prof. Ryan and his colleagues used the two types of stem cells to derive dopamine-producing nerve cells from them.

Then, they exposed these dopaminergic neurons which are known to be affected the most by Parkinsons disease to the two pesticides.

Signs Of Parkinsons Disease

Parkinsons symptoms can be divided into two categories: motor symptoms and non-motor symptoms. Motor symptoms involve changes in how you move your body, and non-motor symptoms are other symptoms not related to movement. Both types of symptoms can be equally difficult to deal with. Until recently, doctors primarily focused on treating motor symptoms. Symptoms can vary in how severe they are from day to day you might feel better one day and worse the next, or even better in the morning and worse later in the day. Severity also depends on how effective your medications are.

What Did The Research Involve

Initially the researchers tested different molecules that fungi release into the air to see how toxic they were. They did this by exposing Drosophila flies to five different molecules. The most toxic was called 1-octen-3-ol.

At high levels it caused damage to the dopamine system in the Drosophila flies brains.

They then took two groups of healthy flies and exposed one group to low dose 1-octen-3-ol, similar to that found in mouldy environments. The other group was the control group and were left in normal air conditions. They measured any changes in movement of the flies and how long it took for them to die.

They then exposed more flies to 1-octen-3-ol and dissected their brains after 24 hours to look for any effect on the dopamine system.

In order to produce some applicability to humans, they also measured the effect of exposure to different strengths of 1-octen-3-ol on the dopamine system in human embryonic kidney cells in the laboratory.

Furthermore, the researchers looked at different genetic types of neurotransporters in the flies brains to see if this changed the effects of the fungi chemical exposure on dopamine transport.

Neurotransporters are specialised proteins involved in the transportation of neurotransmitters through the brain and nervous system.

This was done because some people also have the same genetically different dopamine transporters as found in some flies.

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Neurotoxicity Of Pq Mptp And Other Dopamine Congeners

Several studies suggest that systemic administration of PQ can cause neuronal damage and a parkinsonian-like syndrome in experimental animals . The linking mechanism between PQ exposure and Parkinsons disease is suggested by the alleged chemical similarity between this compound and others known to cause a parkinsonian syndrome, particularly MPTP. MPTP can reproduce most of the biochemical, neuropathological and clinical characteristics of human parkinsonism in both human and non-human primates, with the notable exception of Lewy body formation. MPTP toxicity has been studied in cell systems in mice and in non-human primates. In rats, dopaminergic neurodegeneration is observed at high doses, whereas mice have become the most commonly used species for MPTP studies as they develop a dopaminergic degeneration that may be related to human parkinsonism.

Figure 1

Mechanisms of PQ and MPTP toxicity. PQ can cause an oxidative stress either intracellularly by redox cycling or by activation at cell surfaces by the NADPH oxidase . Mitochondria can be affected indirectly or directly by PQ. In neurons the effects of PQ are believed to be primarily cytosolic. MPTP is converted to its toxic metabolite MPP+ and then sequestered through the dopamine transporter in dopaminergic neurons in which it primarily affects complex I, promoting oxidative stress and mitochondrial damage

It is apparent from this analysis that the initial targets and toxicity mechanisms of PQ and MPP+ differ .

New Proof Of Environmental Link To Parkinsons Disease

Braak

Researchers based their study on previous findings that show exposure to environmental toxins may raise the risk of developing the disease by increasing the rate of oxidative stress. Oxidative stress is related to the bodys ability to eliminate free radicals in the body and can result in cell damage within the body.

In the study, researchers showed that flies lacking forms of the DJ-1 gene were normal under standard conditions. But when they were exposed to high doses of the herbicide paraquat and insecticide rotenone, which have previously been linked to Parkinsons disease, the flies suffered from extreme oxidative stress and died.

Researchers say these findings suggest that a loss of DJ-1 gene function increases sensitivity to chemicals that cause oxidative stress.

Together, researchers say the results shed new light on the biological connections between the inherited and sporadic forms of Parkinsons disease and may lead to more effective treatments.

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Lack Of Exercise/physical Activities

The idea that exercise might have a role in Parkinsons disease is not new. Researchers have been trying to find a connection between Parkinsons and exercise for many years. They think that those who do regular exercise are less likely affected by the disease than those who dont.

A study published in the Journal of Neurology suggests that higher levels of physical activity may reduce the risk of developing Parkinsons disease. In this study, 125,828 provided information on physical activity in early adulthood. During the follow-up, a total of 387 Parkinsons cases were identified. The study found that the people who didnt develop the disease were mostly involved in some sort of higher levels of physical activity.

Similarly, one meta-analysis that included data from 8 prospective studies has concluded that moderate to vigorous physical activity may have an inverse relationship with a risk of Parkinsons.

Although it is not known how exercise could protect someone from developing Parkinsons, researchers think that it may inhibit abnormal changes in dopamine neurons and contribute to the healthy functioning of brain parts involved in body movement.

Watery Or Irritated Eyes

When allergens are present, the body releases histamines as part of its immune response. This histamine release is what causes the eyes to water excessively when exposed to toxins from mold.

This reaction from histamine may be the bodys way of flushing out allergens and toxins. It can serve as a warning to you that your environment may contain dangerous black mold.

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Translating Certainty Ratings Into Levels Of Evidence For Parkinsonian

Five descriptors will be used to rate the level of evidence: high,moderate,low,inadequate evidence, and evidence of no health effect. The first three descriptors used in the previous step to indicate the certainty of the evidence will be directly converted into levels of evidence. However, if the level of certainty is very low or no evidence is identified, the level of evidence will be considered inadequate .

The descriptor evidence of no health effect that indicates that paraquat is not related to PD in humans or in rodent models will be considered only when the level of certainty is high .

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Ask Us For A Recommendation

Botulinum Toxin in Parkinson Disease Tremor & an Injection Approach

Best neuro-protective foods and supplements.

You may ask us about:

  • Supplements scientifically shown to replenish glutathione levels to protect against cell death and toxins
  • Glutathione-building supplement for detoxifying metals and pesticides

We hope that you have been inspired for better Parkinson Disease treatments with natural help.

  • Knowing that yes, that environmental toxins lead to Parkinson is hopefully less scary, because there are prptective foods and supplements.
  • For your best shot at a Parkinson cure, you will want to add the best foods and supplements shown to be neuro-protective.

Metals such as iron are usually high in the brains of Parkinsons patients. Iron can be reduced in the body by:

  • not taking iron supplements
  • eating less red meat
  • drinking green tea and adding curcumin to your food. These contain natural iron-chelating, substances molecules that bind to and remove iron.

Knowing the causes Parkinson Disease will hopefully help live a fuller and longer life!

1. Int J Mol Sci. Parkinsons Disease: From Pathogenesis to Pharmacogenomics 2017 Mar 18: 551. Published online 2017

2. Front Neurosci. Neurochemical and Behavior Deficits in Rats with Iron and Rotenone Co-treatmen. 2017 Nov 23 11:657. doi: 10.3389/fnins.2017.00657. eCollection 2017.

3. PARKINSONS DISEASE: A SYNDROME NOT ADISEASE Issue: BCMJ, vol. 43 , No. 3, April 2001 , Pages 129-132Clinical Articles By: Donald B. Calne, OC, DM

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How Does Paraquat Cause Parkinsons Disease

Paraquat kills cells through a mechanism called oxidative stress, meaning that altered cell chemistry leads to cell damage and death. Parkinsons disease results from the loss of function in the dopamine neuron cells of the substantia nigra pars compacta, a small region of the brain. These neurons may be more vulnerable to oxidative stress than other neurons, and thus more affected by Paraquat, particularly in people with a genetic susceptibility. Not everyone who is exposed to Paraquat develops Parkinsons disease, nor does everyone with a genetic susceptibility.

Only a small number of Parkinsons disease cases are genetic or inherited. As with many diseases, there likely is an interaction between environmental exposures and genetics that leads to the disease.

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Age And Genetic Factors Are Not Everything

The rate of Parkinsons disease globally has exceeded far faster than the population has aged according to the American Parkinson Disease Association.

Cases of the disease are up by several multiples over the past decades. From 1990 to 2015, the cases of the disease globally more than doubled, suggesting that there is far more at work. From 2015 to 2040, cases are expected to double once again. This is far higher than the rate of aging in the population.

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Veterans Exposed To Toxic Chemicals At Military Bases Risk Developing Parkinsons

Accumulating evidence suggests that long-term exposure to trichloroethylene may cause deficits in energy, mood, memory, attention, and psychomotor functioning. In addition, some research suggests that exposure to TCE is associated with a significantly increased risk of Parkinson’s diseasea nervous system disorder that deteriorates a persons ability to control their movement over time.

Parkinsons disease can be difficult to initially detect as early symptoms are subtle and occur gradually. Unfortunately, no cure for Parkinsons disease exists today, but treatments are available to help relieve the symptoms and maintain a good quality of life.

Researchers based their studies on previous findings, which show that exposure to environmental toxins may raise the risk of developing the disease by increasing the rate of oxidative stressan imbalance between free radical activity and antioxidant activity, which can lead to cell and tissue damage. Oxidative stress plays an important role in the degeneration of dopamine-producing neurons leading to neurological conditions, such as Parkinson’s disease.

Exposure To Pesticides In The Military

Environmental Factor

Agent Orange was an herbicide that US troops sprayed in Vietnam from 1961-1971 to kill trees and crops that provided protection and food to the rival army. It is a mixture of two chemicals: 2,4-Dichlorophenoxyacetic acid and 2,4,5-Trichlorophenoxyacetic acid. Agent Orange was also contaminated with Dioxin, a chemical even more damaging than Agent Orange itself, since it is very long-lasting.

The effects of Agent Orange on both the Vietnamese population and on American soldiers has been studied extensively, but with much variability in the results. Birth defects have been attributed to Agent Orange exposure, as well as multiple types of cancer.

With the understanding that the Veteran community served selflessly on behalf of the American people and therefore deserve the protection and support of the American government, the Agent Orange Act was passed in 1991, allowing the Department of Veteran Affairs to declare certain conditions presumptive to exposure to Agent Orange, even if the scientific data associating Agent Orange with that condition was not airtight.

The list of conditions has grown over the years, and in 2010, PD was added. Read here about how veterans who may have been exposed to Agent Orange and have subsequently developed PD are eligible for VA healthcare and disability compensation. APDA offers a free booklet specifically for veterans to help them find the care and support they need.

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No One Definitive Cause Of Parkinsons

There are no biomarkers or objective screening tests that indicate one has Parkinsons. That said, medical experts have shown that a constellation of factors are linked to it.

Parkinsons causes are likely a blend of genetics and environmental or other unknown factors. About 10 to 20 percent of Parkinsons disease cases are linked to a genetic cause, says Ted Dawson, M.D., Ph.D., director of the Institute for Cell Engineering at Johns Hopkins. The types are either autosomal dominant or autosomal recessive .

But that leaves the majority of Parkinsons cases as idiopathic, which means unknown. We think its probably a combination of environmental exposure to toxins or pesticides and your genetic makeup, says Dawson.

Age. The biggest risk factor for developing Parkinsons is advancing age. The average age of onset is 60.

Gender. Men are more likely to develop Parkinsons disease than women.

Genetics. Individuals with a parent or sibling who is affected have approximately two times the chance of developing Parkinsons. Theres been an enormous amount of new information about genetics and new genes identified over the past 10 or 15 years that have opened up a greater understanding of the disease, says Dawson.

Parkinsonism Vs Parkinsons Disease

Parkinsonism refers to a cluster of symptoms that mimic the movement problems caused by Parkinsons disease. Its sometimes referred to as atypical Parkinsons disease, secondary parkinsonism, or Parkinsons plus.

Parkinsons disease is a chronic, neurodegenerative brain disorder. In addition to problems with movement, Parkinsons disease causes non-motor symptoms that arent caused by drug-induced parkinsonism. They include:

Another key difference between drug-induced parkinsonism and Parkinsons disease is symmetry. Drug-induced parkinsonism usually affects both sides of the body equally. Parkinsons disease affects one side of the body more than the other.

Parkinsonism can be caused by medications, repeated head trauma, and environmental toxins. It can also be caused by neurological disorders, including Parkinsons disease. Other neurological conditions that cause parkinsonism include:

  • progressive supranuclear palsy

These medications dont cause resting tremors. Rather, they cause:

  • Action tremors. These occur in a body part thats moving, not a body part thats resting.
  • Postural tremors. These occur when a body part is forced to withstand gravity, such as when arms are outstretched or legs are raised.

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How Environmental Factors Could Cause Parkinsons Disease

Scientists differ about the extent that brain cells are impacted by environmental factors. However, the statistics associated with the disease show that the environment can play a very large role in whether parkinsons disease develops.

Most often, it is exposure to toxic chemicals that could play a role in the development of Parkinsons disease. Usually, these combine with genetic factors to produce the conditions that cause Parkinsons.

Increasing scientific evidence suggests that Parkinsons may be caused by environmental factors such as exposure to herbicides such as Paraquat.

What Do We Know Now About Environmental Factors And Pd

Does Paraquat Exposure Cause Parkinson’s Disease?

In the past two decades, scientists have identified over a dozen environmental factors associated with the risk of developing PD, and for a majority, findings are reasonably consistent across studies . Examples include inverse associations with smoking , coffee drinking , vigorous exercise , ibuprofen use , and plasma urate , as well as positive associations with overall pesticide exposure , use of specific pesticides , and traumatic brain injury . For most of these associations, plausible biological hypotheses have been proposed. However, causal inference for these epidemiological findings has been very difficult. Apart from limited and often inconsistent experimental data, for most of these epidemiological observations, reverse causation is a viable potential explanation that PD development prior to clinical diagnosis changes lifestyle and behavior rather than the other way around. Possible exceptions are the use of certain pesticides. For example, epidemiological findings on rotenone and paraquat are supported by strong experimental evidence, so much so that these chemicals are being used to generate rodent models for PD therapeutic research . Even for pesticides, there are many important questions unanswered. Therefore, despite its importance and a reasonable accumulation of literature, our understanding of environmental contributions to PD is still in its infancy.

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Rotenone: From Pesticide To Modeling Pd

Among the toxic animal models of PD, rotenone represents one of the most recently used approaches.91 Rotenone is the most potent member of the rotenoids, a family of natural cytotoxic compounds extracted from various parts of Leguminosa plants. Rotenone’s chemical structure is presented in Figure 3.

Chemical structure of rotenone.

In contrast to the 6-OHDA and MPTP models, in rotenone-infused rats, some of the remaining substantia nigra dopaminergic neurons contain proteinaceous inclusions.91,109,110 Like LBs in PD, these inclusions are immunoreactive for both ubiquitin and -synuclein,91 and by electron microscopy they appear composed of a dense core with fibrillar peripheral elements.91 Likewise in PD in which neurodegeneration extends beyond the dopaminergic system,77 rotenone infusion is associated with 35% reduction in serotonin transporter density in the striatum, 26% reduction of noradrenergic neurons in the locus coeruleus, and 29% reduction in cholinergic neurons in the pedunculopontine nucleus.110

Based on this review, it may be concluded that the chronic administration of rotenone has still a long way to go to become a routine PD model, due to its inconsistent and unpredictable effect on the nigrostriatal pathway. Unless these problems are resolved, it is unlikely that preclinical neuroprotection studies could be carried out successfully in such a model.

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