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This post is more on the theme of nanoparticles and human health. My last post was about a study that examined how inhaled nanoparticles  (for example, from air pollution) travel from the lungs to the bloodstream. Well, today's post is about a pretty shocking 2016 air pollution nanoparticle study which examined the brains (brain tissue) of 45 dead people  (ages 3 to 92) who had lived for a long time in two places with heavy  particulate air pollution - Mexico City and Manchester, England. Some of the British people also had Alzheimer's disease or dementia.

The researchers found evidence that minute nano-sized particles of magnetite from air pollution can find their way into the brain. There are 2 forms of magnetite (which is an iron ore) - one naturally occurring (jagged edges in appearance), and one found commonly in air pollution (smooth and rounded - from being created in the high temperatures of vehicle engines or braking systems). The researchers are concerned that the air pollution nanoparticles may increase the risk for brain diseases such as Alzheimer's.

One of the researchers (Prof Barbara Maher) has previously identified magnetite particles in samples of air gathered beside a busy road in Lancaster, England and outside a power station. She suspected that similar particles may be found in the brain samples, and that is what happened. "It's dreadfully shocking. When you study the tissue you see the particles distributed between the cells and when you do a magnetic extraction there are millions of particles, millions in a single gram of brain tissue - that's a million opportunities to do damage."..."It's a whole new area to investigate to understand if these magnetite particles are causing or accelerating neurodegenerative disease." However, it must be stressed that at this time there is no proven link between these magnetite particles and any neurodegenerative diseases. They're just wondering.... they call finding these pollution nanoparticles "suggestive observations".

From Medical Xpress: Toxic air pollution nanoparticles discovered in the human brain

Tiny magnetic particles from air pollution have for the first time been discovered to be lodged in human brains – and researchers think they could be a possible cause of Alzheimer's disease. Researchers at Lancaster University found abundant magnetite nanoparticles in the brain tissue from 37 individuals aged three to 92-years-old who lived in Mexico City and Manchester. This strongly magnetic mineral is toxic and has been implicated in the production of reactive oxygen species (free radicals) in the human brain, which are associated with neurodegenerative diseases including Alzheimer's disease.

Professor Barbara Maher, from Lancaster Environment Centre, and colleagues (from Oxford, Glasgow, Manchester and Mexico City) used spectroscopic analysis to identify the particles as magnetite. Unlike angular magnetite particles that are believed to form naturally within the brain, most of the observed particles were spherical, with diameters up to 150 nm, some with fused surfaces, all characteristic of high-temperature formation – such as from vehicle (particularly diesel) engines or open fires. The spherical particles are often accompanied by nanoparticles containing other metals, such as platinum, nickel, and cobalt.

Professor Maher said: "The particles we found are strikingly similar to the magnetite nanospheres that are abundant in the airborne pollution found in urban settings, especially next to busy roads, and which are formed by combustion or frictional heating from vehicle engines or brakes."

Other sources of magnetite nanoparticles include open fires and poorly sealed stoves within homes. Particles smaller than 200 nm are small enough to enter the brain directly through the olfactory nerve after breathing air pollution through the nose.....The results have been published in the paper 'Magnetite pollution nanoparticles in the human brain' by the Proceedings of the National Academy of Sciences.

A good discussion of the study in The Scientist: Environmental Magnetite in the Human Brain

Image of magnetite nanoparticles from the exhaust plume of a diesel engine. Credit Maher et al study, 2016.

 

 

A microscopic image shows magnetite nanoparticles in the human brain. Barbara Maher et al study, 2016.

 

 

A study by researchers showing troubling effects from certain pesticides (especially a class of fungicides) raises all sorts of questions: What is the long-term effect of chronic low doses of these fungicides in the foods we eat? How much of these chemicals are we getting exposed to? The Univ. of North Carolina researchers studied the effect of 294 chemicals (all common food-use pesticides or other environmental chemicals) on "mouse cortical neurons" (mouse brain cells). They found that one group of chemicals, which they referred to as "cluster 2", "mimics brain disorders" such as autism, advanced age, Alzheimer's, Parkinson's disease, and other neurodegenerative disorders. The chemicals (all pesticides, and mainly fungicides) causing these effects are: fenamidone, pyraclostrobin, famoxadone, trifloxystrobin, fenpyroximate, azoxystrobin, fluoxastrobin pyridaben and rotenone. Even though this study was done on mouse cortical neurons (in vitro), it is meaningful because of the similarities with human brain cells.

Very little is known about human exposure to these chemicals (how much is our exposure?) and their effects on humans, but the data suggest effects similar to that in neurological disorders. The researchers point out that many of the chemical residues in this cluster were found on conventionally raised foods, especially leafy green vegetables, and were detected at relatively high levels, especially pyraclostrobin. Most of these fungicides only came into use after 2000 and usage of these fungicides has been increasing in the U.S, with the exception of pyridaben (decreasing use) and rotenone (very low use). "These data suggest significant human exposure potential to many of the chemicals in cluster 2".

They point out that these fungicide residues have not been detected on organically produced foods (EPA and USDA data), which suggests a way to minimize exposure. None of these chemicals can be used by organic farmers in the U.S. Possible exposure is also from gardens and lawns (if used), contaminated water, and for farm workers in conventional agriculture. From Science Daily:

Could new class of fungicides play a role in autism, neurodegenerative diseases?

Scientists at the UNC School of Medicine have found a class of commonly used fungicides that produce gene expression changes similar to those in people with autism and neurodegenerative conditions, including Alzheimer's disease and Huntington's disease.

Mark Zylka, PhD, senior author of the study and associate professor of cell biology and physiology at UNC, and his team exposed mouse neurons to approximately 300 different chemicals.... "Based on RNA sequencing, we describe six groups of chemicals," Zylka said. "We found that chemicals within each group altered expression in a common manner. One of these groups of chemicals altered the levels of many of the same genes that are altered in the brains of people with autism or Alzheimer's disease." Chemicals in this group included the pesticides rotenone, pyridaben, and fenpyroximate, and a new class of fungicides that includes pyraclostrobin, trifloxystrobin, fenamidone, and famoxadone. Azoxystrobin, fluoxastrobin, and kresoxim-methyl are also in this fungicide class.

"We cannot say that these chemicals cause these conditions in people," Zylka cautioned. "Many additional studies will be needed to determine if any of these chemicals represent real risks to the human brain." Zylka, a member of the UNC Neuroscience Center, and his group found that these chemicals reduced the expression of genes involved in synaptic transmission -- the connections important for communication between neurons. If these genes are not expressed properly, then our brains cannot function normally. Also, these chemicals caused an elevated expression of genes associated with inflammation in the nervous system. This so-called neuroinflammation is commonly seen in autism and neurodegenerative conditions.

The researchers also found that these chemicals stimulated the production of free radicals -- particles that can damage the basic building blocks of cells and that have been implicated in a number of brain diseases. The chemicals also disrupted neuron microtubules. "Disrupting microtubules affects the function of synapses in mature neurons and can impair the movement of cells as the brain develops," Zylka said. "We know that deficits in neuron migration can lead to neurodevelopmental abnormalities. We have not yet evaluated whether these chemicals impair brain development in animal models or people."

Jeannie T. Lee, MD, PhD, professor of genetics at Harvard Medical School and Massachusetts General Hospital, who was not involved in this research, said, "This is a very important study that should serve as a wake-up call to regulatory agencies and the general medical community. The work is timely and has wide-ranging implications not only for diseases like autism, Parkinson's, and cancer, but also for the health of future generations. I suspect that a number of these chemicals will turn out to have effects on transgenerational inheritance."

Zylka's group also analyzed information from the U.S. Geological Survey, which monitors countywide pesticide usage, as well as the Food and Drug Administration and the U.S. Department of Agriculture, which test foodstuffs yearly for pesticide residues. Of the chemicals Zylka's team studied, only the usage of pyridaben has decreased since 2000. Rotenone use has remained the same since 2000. However, the use of all the fungicides in this group has increased dramatically over the past decade.

Indeed, a study from the Environmental Protection Agency found that pyraclostrobin is found on foods at levels that could potentially affect human biology, and another study linked pyraclostrobin usage to honeybee colony collapse disorder. The pesticide rotenone was previously implicated in Parkinson's disease through replicated animal experiments and through human epidemiological studies.....Previous work has also shown that a single dose of the fungicide trifloxystrobin reduced motor activity for several hours in female rats and for days in male rats. Disrupted motor function is a common symptom of Parkinson's disease and other neurological disorders. The related fungicide picoxystrobin impaired motor activity in rats at the lowest dose tested.

Zylka added, "The real tough question is: if you eat fruits, vegetables or cereals that contain these chemicals, do they get into your blood stream and at what concentration? That information doesn't exist." Also, given their presence on a variety of foodstuffs, might long term exposure to these chemicals -- even at low doses -- have a cumulative effect on the brain?

Zylka noted that conventionally grown leafy green vegetables such as lettuce, spinach, and kale have the highest levels of these fungicides. But due to each chemical's effectiveness at reducing fungal blights and rust, crop yields have increased and farmers are expanding their use of these chemicals to include many additional types of food crops.

Zylka's team hopes their research will encourage other scientists and regulatory agencies to take a closer look at these fungicides and follow up with epidemiological studies. "Virtually nothing is known about how these chemicals impact the developing or adult brain," Zylka said. "Yet these chemicals are being used at increasing levels on many of the foods we eat."

Applying fungicide to apple orchard. Credit: Univ. of Kentucky Agriculture Extension

Could this be? Fungal infection being the cause of Alzheimer's disease? Noteworthy from a recent study conducted in Spain: all the Alzheimer's disease (AD) patients had evidence of fungal infections in their brains, central nervous systems, and vascular systems, but none were found in the control subjects (those without Alzheimer's disease). Many of the symptoms of AD (such as inflammation of the central nervous system and activation of the immune system) match those with long-lasting fungal infections. A "microbial cause" has long been suggested as a cause of AD, and interestingly other studies have also found fungal infections in AD patients. The research so far has found several fungal species in AD patients (including Candida albicans). The researchers mention that in one study anti-fungal treatment reversed clinical symptoms of AD in 2 patients (but it was written off  as misdiagnosis).

Another possibility that immediately occurs to  explain the findings is that perhaps Alzheimer's disease somehow results in fungal infections - that the AD makes them more prone to fungal infection. In case you're wondering - all the AD patients and control patients studied had died - this is why their brain tissue could be studied so thoroughly. Excerpts from a research article by D. Pisa et al in Nature:

Different Brain Regions are Infected with Fungi in Alzheimer’s Disease

The possibility that Alzheimer’s disease (AD) has a microbial aetiology has been proposed by several researchers. Here, we provide evidence that tissue from the central nervous system (CNS) of AD patients contain fungal cells and hyphae. Fungal material can be detected both intra- and extracellularly using specific antibodies against several fungi. Different brain regions including external frontal cortex, cerebellar hemisphere, entorhinal cortex/hippocampus and choroid plexus contain fungal material, which is absent in brain tissue from control individuals. Analysis of brain sections from ten additional AD patients reveals that all are infected with fungi. Fungal infection is also observed in blood vessels, which may explain the vascular pathology frequently detected in AD patients. Sequencing of fungal DNA extracted from frozen CNS samples identifies several fungal species. Collectively, our findings provide compelling evidence for the existence of fungal infection in the CNS from AD patients, but not in control individuals.  ...continue reading "Fungal Infections Involved in Alzheimer’s Disease?"