Tuesday, October 4, 2022

Environmental Causes Of Parkinson’s Disease

Genetic And Environmental Factors Affect Gut Microbiota

Environmental Factors in Parkinson’s Disease with Harvey Checkoway – On Our Mind

The gut microbiota is a dynamic microbial system, and it can be modified by genetic and environmental factors. Previous studies have reported that the gut microbiota is constantly challenged by environmental factors such as exercise, diet, stress, altitude, temperature, toxicants/pollutants, and noise,. Environmental contaminants can affect the composition of the gut microbiota, leading to physiological disorders in the host and causing certain diseases. The gut microbiota has become a new toxicological target for some environmental pollutants. A decreasing diversity of gut microbiota is often observed after exposure to heavy metals. In our previous studies, Mn exposure led to decreased abundances of Prevotellaceae, Fusobacteriaceae, and Lactobacillaceae,. In addition, Nasuti et al. showed that changes in gut microbiota may be one of the reasons for the neurotoxicity of permethrin. Many studies have shown that antibiotic administration leads to disturbances in the microbial diversity and metabolism of the gut microbiome that might be linked to a multitude of diseases.

Genetic And Environmental Risk Factors For Neurodegenerative Diseases

Mutations in the gene encoding leucine-rich repeat kinase 2 are the most common cause of hereditary PD. LRRK2 activity promotes -synuclein propagation via the phosphorylation of RAB35. A genetic component for the apparently sporadic disease was not obvious in the early days of PD research. LRRK2 mutations can cause familial PD with age-dependent but variable penetrance variants of the gene are also risk factors for sporadic PD. Individuals with mutations in the genes PARKIN, PINK1, SNCA, GBA1, and LRRK2 show an increased risk of developing familial PD . In addition, multiple mutations in genes such as C9orf72, TARDBP, and SOD1 are mainly expressed in a variety of nonneuronal cells which enhance immune dysregulation and neuroinflammation in the pathogenesis of ALS.

Fig. 3: Implications of metals in A neurotoxicity.

APP binds to metals . Under acceleratory conditions, A self-aggregates and forms several types of oligomers finally forming insoluble aggregates , and tight binding to the surface of neurons and form fibrillar deposits.

We Know Age And Genetics Play A Role In Parkinsons But How Does The World We Live In Impact On Our Risk Of Developing The Condition

Parkinsons is a neurodegenerative condition affecting around 145,000 people in the UK. It develops when dopamine-producing cells in the brain stop working properly and, over time, are lost.

This much we know. But what we dont know is what actually causes Parkinsons. Its often referred to as idiopathic Parkinsons, which translates from the original Greek as a disease of its own kind the cause is unknown.

Age is the biggest risk factor most people who get Parkinsons are aged 50 or over. As we age, damaging molecules called free radicals build up inside our bodies, causing the cells to become stressed. Energy-producing mitochondria may stop working properly, damaged proteins may accumulate, and, over time the cells may die. Research has shown that dopamine-producing brain cells seem to be particularly vulnerable to these changes seen with ageing, increasing the risk of Parkinsons as we get older.

But, age isnt the only player at the table. People under the age of 50 can get Parkinsons too. This early onset Parkinsons is often linked to very rare changes in certain genes, such as those involved in removing damaged proteins and helping mitochondria to work properly.

In this blog, well specifically investigate environmental factors in more detail.

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Now Is A Major Opportunity To Move Forward

Although still somewhat controversial, the Braak hypothesis presents a unique hypothetical framework of PD development that may allow us to better conceptualize steps of PD prodromal development and environmental contributions. According to this hypothesis, PD Lewy pathology develops in six sequential stages, first in the olfactory bulb or enteric nerves , years if not decades, before spreading to the substantia nigra where dopaminergic neuron death occurs . In support of this hypothesis, recent clinical and epidemiological studies have clearly documented a wide range of nonmotor symptoms in PD patients, and some symptoms such as olfactory impairment , REM sleep behavior disorder , and constipation may have developed years, if not decades, prior to PD clinical diagnosis. While there are still substantial challenges to adequately define prodromal PD, by using these symptoms as noninvasive intermediate phenotypes, we may be able to bring new insights into this black-box of PD prodromal development by identifying factors that initiate PD pathogenesis, lead to these intermediate phenotypes, or modify progression to clinical PD . This framework may fundamentally improve understanding of PD prodromal development and contributions from environmental factors.

What Causes Parkinsons Disease

PPT

Parkinsons disease is a chronic, progressive neurological disease that currently affects about 1 million Americans. Parkinsons disease involves a small, dark-tinged portion of the brain called the substantia nigra. This is where you produce most of the dopamine your brain uses. Dopamine is the chemical messenger that transmits messages between nerves that control muscle movements as well as those involved in the brains pleasure and reward centers. As we age, its normal for cells in the substantia nigra to die. This process happens in most people at a very slow rate.

But for some people, the loss happens rapidly, which is the start of Parkinsons disease. When 50 to 60 percent of the cells are gone, you begin to see the symptoms of Parkinsons.

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Paraquat Can Kill Instantly

One study on the paraquat link to Parkinson’s found that 3 of 544 cases of Parkinson’s disease were associated with paraquat inhalation. All three sufferers had a history of contact with the herbicide before their diagnosis.

Unlike other herbicides, this weed and grass killer can kill a subject instantly when swallowed or cause Parkinson’s disease through long-term exposure.

Over time, slowed mobility and stiffness develop in the patient. Parkinson’s disease gradually progresses since it has five stages. The earlier stages are less noticeable, but the victim’s quality of life and mobility suffer as they go to the later stages.

Here are some motor and non-motor symptoms of Parkinson’s disease patients experience:

  • Change in speech patterns and general speech
  • Hunching forward
  • Frequent shaking and tremors in hands
  • Notably slow mobility

A 2018 study found that farmworkers using hazardous Paraquat were 2.5 times more likely to suffer serious health problems and develop Parkinson’s disease.

Lewy Pathology In Enteric Nervous System

The Lewy pathology has been identified in the gastrointestinal tract on an average of 7 years before the onset of the motor symptoms . BRAAK in 2006 put forward a hypothesis that the pathology of PD may be initiated from the gut and then the pathological substances transported from the gut to the brain. Subsequently, several studies presented evidence to support this hypothesis. Animal studies demonstrated that the intragastrically administered rotenone, a PD inducer, could cause pathological -synuclein formation in ENS, in the vagal nerve, and then the brainstem. When vagotomy was performed, the pathological -synuclein stopped transporting to the brain . Furthermore, human -synuclein injected into the intestinal wall of healthy mice could transport via the vagal nerve and reach the brainstem . Interestingly, cohort studies found that compared to controls, patients receiving truncal vagotomy had a decreased risk of PD vagotomy referring to resecting the vagal nerve, is a treatment for peptic ulcers. The above-mentioned studies provide evidence for the hypothesis that Lewy pathology may be initiated in ENS and move toward the SNpc and other parts of the CNS .

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Environmental Risk Factors And Parkinsons Disease: An Umbrella Review Of Meta

We assessed the strength of the evidence linking 75 environmental risk factors with Parkinsons disease.

Physical activity and constipation presented Class I evidence for an association.

Head injury, anxiety or depression, beta-blockers, smoking, and serum uric acid presented Class II evidence for an association.

The majority of the examined meta-analyses had large or very large heterogeneity, many had signals of bias, and confounding or reverse causation was a common explanation.

Data from more prospective studies and investigation of sources of heterogeneity are needed to better understand the association between the risk factors and PD.

Parkinsons Disease Risk Factors

Environmental Exposures in Veterans with Parkinson’s Disease

Although a primary cause for Parkinsons disease is yet to be identified, a number of risk factors are clearly evident.

Advancing age Although there is the occasional case of the disease being developed as a young adult, it generally manifests itself in the middle to late years of life. The risk continues to increase the older one gets. Some researchers assume that people with Parkinsons have neural damage from genetic or environmental factors that get worse as they age.

Sex- Males are more likely to get Parkinsons than females. Possible reasons for this may be that males have greater exposure to other risk factors such as toxin exposure or head trauma. It has been theorised that oestrogen may have neuro-protective effects. Or, in the case of genetic predisposition, a gene predisposing someone to Parkinsons may be linked to the X chromosome.

Family history Having one or more close relatives with the disease increases the likelihood that you will get it, but to a minimal degree. This lends support to the idea that there is a genetic link in developing Parkinsons.

Post menopausal who do not use hormone replacement therapy are at greater risk, as are those who have had hysterectomies.

Low levels of B vitamin folate Researchers discovered that mice with a deficiency of this vitamin developed severe Parkinsons symptoms, while those with normal levels did not.

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Reasons Why Parkinsons Disease Occurs

The scientific reason given for Parkinsons disease is that the patient has lost nerve cells in the part of the brain called the substantia nigra. A very important chemical called dopamine is produced by the substantia nigra. The loss of the ability to produce dopamine contributes to the early stages of Parkinsons disease.

Hold Paraquat Manufacturers Accountable

The bad thing about paraquat exposure is that companies knew about its link with Parkinson’s. Still, they continued to make and sell the herbicide. Therefore, paraquat Parkinson’s lawsuits can hold these companies accountable for being negligent.

The herbicide manufacturers knew about Paraquat’s potential links to Parkinson’s. However, they did not warn farmers, landscapers, or other people who used the herbicide about its side effects.

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Is Paraquat Banned In The United States

While many countries in the world have banned paraquat, in the United States, the weed killer is still in use on many farmlands sprayed with the deadly weed and grass killer.

There are no federal or state laws that ban consumers from buying or using paraquat. However, no one can sell the chemical to anyone under 18. In addition, the US Department of Transportation restricts the herbicide to transport on public roadways because of its toxicity.

In the United States, multiple states have issued a ban on paraquat for any agricultural purpose. Using paraquat as an active ingredient against plants and vegetation is illegal.

Two of the states that have banned paraquat:

  • Connecticut
  • Hawaii

Although paraquat has been banned in some states, it is still legal in other states. In the states where paraquat is still legal to use and purchase, federal agencies have restricted its transportation on public roadways due to toxicity concerns.

The paraquat lawyers at Rosenfeld Injury Lawyers represent victims harmed by the toxic chemical, including those diagnosed with Parkinson’s disease.

What Do We Know Now About Environmental Factors And Pd

WONG MEDICAL CENTRE IPOH ?: PARKINSON 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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The Five Environmental Causes Of Parkinsons Disease

Parkinsons disease is a brain disorder that develops and becomes worse over time. The typical symptoms of the disease include tremor, stiffness, slowness of movement, and balance problems. These symptoms develop when the brain lost its ability to produce a sufficient amount of dopamine, a neurotransmitter responsible for controlled body movement.

Researchers have identified a variety of environmental factors that are linked to Parkinsons disease. Some of these factors may directly cause the disease symptoms, others may increase the risk of developing it.

Here are the 5 main environmental factors that are linked to Parkinsons disease development.

Better Parkinson Prognosis With Protection

One of the known markers for PD is low glutathione in the substantia nigra which was also the case for these animals that were given rotenone and iron.

Glutathione is the bodys protective molecule and is typically depleted in the brains of Parkinsons patients.

Increasing glutathione in the substantia nigra, they found, gave the test animals dopaminergic neuroprotection and decreased the damage caused by these toxins.

This molecule can also protect against the eventual toxic effect of the Parkinsons medications which cause dyskinesia or shaking:

See: Dyskinesia caused by Parkinsons Medications, Carbidopa, Levodopa

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Environmental Causes Of Parkinsons Disease

Parkinsons Disease causes are classified as environmental causes due to the fact that they occur through exposure to certain drugs which has been proven in scientific studies.

The most common sign of parkinsonism is a resting tremor, which causes shaking when the individual assumes or is forced into certain positions.

Other less frequent symptoms are impaired movement and balance problems due to changes in muscle stiffness, slow movements, rigidity, sleep disturbances, mood changes, and difficulty speaking or swallowing.

Symptoms worsen with time as the disease progresses to its final stages where it causes an inability to walk, talk, swallow properly, stay awake for a long period of time.

What Causes Parkinsons

Parkinson’s Disease Etiology | Environmental factors | Genetic factors |

Parkinsons is a disease of the central nervous system caused by the loss of dopamine-producing cells in the brain. However, exactly why dopamine-producing cells become lost is unclear. Research suggests that a combination of genetic and environmental factors may be responsible. How these two factors interact varies from person to person. It is also unclear why some people develop the disease but not others.

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What Is Niehs Doing

NIEHS supports diverse research, involving experts from many disciplines, to uncover what may cause or help prevent Parkinsons disease. Varied methods are important because no one can predict which paths of study will provide major breakthroughs. Basic research on Parkinson’s will continue to help us advance our understanding of the disease. Highlights from NIEHS research are described below, grouped by environmental factors that may affect Parkinsons and by research approaches.

Pesticides

Mounting evidence, from animal and human studies, suggests that exposure to certain types of pesticides can increase a persons risk of developing Parkinson’s disease.

Some people are more vulnerable to the harmful effects of pesticides because of their age or genetic makeup.

  • Many studies identified genetic variations that provide insight into why certain people appear to be at higher risk of developing Parkinsons.
  • Using data from the NIEHS-conducted Agricultural Health Study, researchers found that Parkinson’s risk from paraquat use was particularly high in people with a particular variant of a gene known as GSTT1.5
  • Similarly, other research has indicated that people with lower levels of the PON1 gene, which is important for the metabolism of organophosphate pesticides, showed faster progression of the disease.6

Trichloroethylene

Head Injuries

Air Pollution

Diet and Lifestyle

Predicting Disease

Some of the risk factors and premotor symptoms that may be involved in Parkinson’s.

Experts Discuss Monkeypox Symptoms Spread

by Nardy Baeza Bickel, University of Michigan

Monkeypox has been declared a national public health emergency. Two epidemiologists at the University of Michigan School of Public Health discuss the disease and its implications.

Joseph Eisenberg, professor of epidemiology, is an infectious disease epidemiologist studying environmental determinants of infectious disease with a focus on waterborne and vector borne diseases. Andrew Brouwer, assistant research scientist in epidemiology, uses mathematical and statistical modeling to address public health problems in infectious disease, cancer and tobacco control.

Should we be worried now that the monkeypox virus has been declared a public health emergency in the United States?

Brouwer: MPV has been declared a public health emergency by the World Health Organization, the U.S. Department of Health and Human Services, and some states and localities. These declarations serve to bring attention to the topic, enhance coordinated responses, and make money and resources available. It does not mean that we’re all in imminent danger of being infected.

Is monkeypox going to be the next pandemic?

What is monkeypox?

Eisenberg: Monkeypox is a viral disease related to smallpox. It’s different from smallpox in that the disease primarily is spread among nonhuman animals like rodents and primateswhat we call a zoonotic diseaseand historically has been endemic in central and west Africa, primarily in rainforest areas.

How is monkeypox spread?

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