Exposure to Pesticides May Contribute to the Development of Parkinson’s disease

By Roberta Attanasio, IEAM Blog Editor

For the past few years, Parkinson’s disease and its association with exposure to pesticides has been the topic of a hot debate – one after the other, studies have shown a clear epidemiologic link between disease development and pesticide exposure without, however, identifying any related mechanism of action. Finally, in January 2013, results published in the journal Proceedings of the National Academy of Sciences pointed out a mechanism of action for the fungicide benomyl, a persistent pesticide that is still present in the environment despite having been banned by the U.S. in 2001. Now, results from a new study published in the current issue (February 4, 2014) of the journal Neurology show that several additional pesticides may be involved in the development of Parkinson’s disease, with a mechanism similar to that described for benomyl.

Dopamine pathways in the human brain

Dopamine pathways in the human brain, derived by NIDA, Quasihuman, licensed under CC BY-SA 3.0

Parkinson’s disease is a chronic and progressive neurodegenerative disorder that affects nearly one million individuals in the U.S. According to the Parkinson’s Disease Foundation, tell-tale symptoms are tremor of the hands, arms, legs, jaw and face, slowness of movement, stiffness of the limbs and trunk as well as impaired balance and coordination. The disease is primarily caused by the death of neurons located in a specific area of the brain – the substantia nigra. Some of these neurons produce dopamine, a messenger molecule involved in the control of movement and coordination. In individuals with Parkinson’s disease, the decrease in dopamine production caused by neuron death leads to impaired movement and coordination.

Mouse hippocampal neurons taken via brightfield microscopy, by asymptoticdesign, licensed under CC BY-NC-SA 2.0.

As shown in the 2013 study, the fungicide benomyl inhibits aldehyde dehydrogenase (ALDH) – an enzyme that converts aldehydes to less toxic compounds. Aldehydes are highly toxic to neurons that produce dopamine and, therefore, by inhibiting ALDH, benomyl leads to neuron damage.

In the new population-based, case-control, epidemiologic study, the researchers used a test that they developed to identify pesticides able to inhibit the activity of ALDH. They found that several of these pesticides experimentally inhibited ALDH activity in neuronal suspensions, and exposures to these same pesticides were associated with 2- to 6-fold increases in the risk of developing Parkinson’s disease in a human population. These pesticides fell into four classes – dithiocarbamate, imidazole, dicarboxymide, and organochlorine. For all the ALDH-inhibiting pesticides identified in the study, the risk of developing disease increased according to increasing levels of exposure. In addition, the researchers found that the risk of developing disease increased in individuals that are not only exposed to the pesticides, but also possess a genetic variant of the ALDH gene. Interestingly, the association between Parkinson’s disease and genetic variants was observed only when an environmental contribution was also considered.

The study shows that inhibition of ALDH may be an important mechanism contributing to the development of Parkinson’s disease and identifies pesticides that should be avoided to reduce the risk of developing the disorder (these pesticides are clearly listed in the published paper). In addition, the study opens up an intriguing possibility for Parkinson’s patients – that of a potential cure. By eliminating toxic aldehydes or increasing the activity of ALDH, it might be possible to slow or reverse disease progression, and this may be true especially for patients that develop Parkinson’s disease in association with exposure to pesticides.

13 thoughts on “Exposure to Pesticides May Contribute to the Development of Parkinson’s disease

  1. Giovanna

    A good study once more stressing the strict correlation between our environment and our health . It demonstrates an actual mechanism of action for the chemicals studied. and their actions on the cells of the nervous system. Will it have a real impact on pesticides use?

    Reply
  2. awilson

    The links between pesticides and human degenerative diseases are coming to light, finally. Studying these exposures is not easy, there are too many pesticides and people are exposed to them at different concentrations, different mixtures and at different times. The epidemiological evidence is a nice, needed addition, but what makes the studies from this group so strong is the identification of mechanisms. Doing studies to directly prove cause-effect relationships is the necessary step to finally influence policy.

    Reply
  3. Sumith Jayakody

    is carbendazim, which is a metabolic conversion product of benomyl in plants, could lead to this action in humans?

    Reply
    1. Roberta Attanasio

      According to Arthur Fitzmaurice et al. (PNAS, 110, 636-641, 2013), “Benomyl decomposes spontaneously, creating a reservoir for slow release of carbendazim and butyl isocyanate (BIC) ….. The ALDH inhibitory activity is caused by BIC and its downstream metabolites.” Therefore, it appears that carbendazim is not involved in ALDH activity.

      Reply
  4. Yousif O.H. Assad

    The study is fantastic highlight the side effects of the pesticides use to help us but seem to harm us particularly in the third world, also tell the manufacturer to consider humans health in deep, before recommend any chemical for use (instead of just collect money. so many pesticides in use today lacking this type of study), this problem need influence policy to take action.

    Reply
  5. Aaron Peaslee

    I am very aware of the environmental effect of pesticides; however, until now, I was unaware they were linked to Parkinson’s Disease. Unfortunately, I think it will take a lot to influence policy on pesticide use, even with evidence such as this. There’s simply too much lobbying money behind these corporate run farms. If the pesticides in this study are banned, then there will be new ones developed to take their place. Public awareness and education, such as this, are also useful tools in generating more public pressure on our government to hold those that manufacture and use these chemicals responsible. On a more optimistic outlook, this added insight into how the pesticides increase the likelihood of developing PD not only supports the efforts to better regulate chemicals used in agricultural industry, but it also might lead us to other means of developing pesticides that don’t have such harmful ramifications. For example, we now know that any new pesticide under development should be tested for ALDH inhibition. I could easily imagine how, someone more clever and educated than myself, could design pesticides to to become inert in the human digestive system. I would also think that there might be a way to make the pesticide recognizable by the human immune system, such as presenting an antigen. Hopefully as more information like this becomes available, it will drive us to develop better, more innovative, solutions to the problems we face today.

    Reply
  6. Ray Kinney

    If glyphosate primary mode of action is on disruption of the shikamate pathway, and is thought to be generally safe for animal ingestion because animals don’t utilize the shikimate pathway, how much of a risk is posed by potential disruption of gut biota that do utilize the shikamate pathway? Does the acidic gut environment protect from glyphosate effects, or are we risking widespread pathogenic effects from gut assemblage alterations?
    Are the increased allowable levels of glyphosate in foods justified until the possibility is answered definitively?

    Reply
  7. Roberta Attanasio

    These are very important questions that (I guess) will be explored in the next few years as the role of the microbiota and the value of our symbiotic relationship with microorganisms become fully appreciated.

    Reply
  8. cns2392

    I don’t think there is any surprise to anyone that pesticides have a negative effect on our health. However, pesticide use (as well as fungicides and other chemicals) are becoming more and more popular. As a correlation to Parkinson’s is being discovered, what other irreversible health concerns might we come to expect? I also question at what dosage/exposure level do these chemicals become toxic? Is there a happy medium where farmers can use just enough, yet the toxicity level be minimal and not detrimental to our health? Or are there natural methods or products that act as pesticidal substances?

    Reply
    1. Ray Kinney

      Most pesticides, degradates, and metabolites are toxic at any level. There are rarely any actual thresolds of effect adequately discovered that would indicate ‘no adverse effect’
      Our ability to discern the subtle, subclinical degradations of health just keeps clarifying that supposed ‘thresholds’ are illusory, and if we look deeper into the pathology spectrum we will find more harm. Creeping ‘normalization of acceptance’ of body contaminant levels as many of the eightyfive thousand new chemicals we have created get dispersed (without adequate ecotoxicologic assessment on almost all of them) hides pervasive unrecognized public health harm, both additively and synergistically. We really know so little about how we are harming ourselves, PD is the tip of the toxic iceburg. We smugly suppose that we know much more than we actually do, and our regulatory ‘expertice’ is woefully inadequate.
      We are in deep doo doo. IMHO

      Reply
      1. Ray Kinney

        A finding of no adverse effect level is usually dependent on assessment of single pathogen effects in a lab, but the real world is messier and an effect that is ‘less than creating adverse effect’ may in fact be potentiating the pathogenic involvement of numerous toxicants present, but all perhaps at levels that individually would not trigger a finding of ‘adverse effect’ designation…. yet a medical problem could result never the less.

        Reply
  9. Olumba Obu

    Because dopamine does not cross the blood -brain barrier it specifically facilitates neural function. As i learned in my Hormones and Behavior class, dopamine is usually converted into epinephrine which is thus secreted by the adrenal madulla. Nonetheless Parkinson’s Disease can be very detrimental to not only to brain function but immune response as well. I also believe that it is important to eliminating toxic aldehydes because ALDH assist in proper metabolism of the body’s muscles and heart.

    Reply
  10. Ray Kinney

    Lots of substances cross the blood brain barrier when the barrier is compromised. An example is found in levels of the toxic metal lead that contact lipids in the membane of the bbb. Peroxidation reactions can damage the protective membrane and allow access to lead and other toxins normally kept out. Lead can potentiate other neurotoxicants by creating more access to the CNS. The lead may perforate the bbb and allow chronic body accumulations of the cyanobacterial derived BMAA toxin higher brain contact, or allow MSG-derived circulating glutamate better access to motor neurons, with possibly increased NMDA receptor disregulation, calcium flow through cell walls, excitotoxic free glutamate residence time in the synaptic cleft and reduced protective glial function for sequestering the glutamate. Meanwhile the increased lead brain levels can also reduce GABA by up to 60%, and glutathione , which has many implications for further pathology. PD is probably a result of all of these neurotoxin accumulative effects, in various combinations and levels. Pesticide associations with PD, and other neuro diseases including ALS may just add further potentiation. In the real world outside of the labs, it is this type of multiple toxicant exposure scenario that is made up of numerous ‘associations’ but the ‘causative agent’ is not likely to be a single exposure. The labs need oversimplification to do science, yet the real world of toxicity in the brain is what needs complex characterization for understanding of causative assessment. All of these toxicants, and more, are being researched heavily for PD, but it is not likely that only one is ever going to be declared ‘the cause of PD’. IMHO

    Reply

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