Stopping cholesterol drugs may be associated with increased risk of Parkinson’s

Contact: Rachel Seroka rseroka@aan.com 612-928-6129 American Academy of Neurology

MINNEAPOLIS – People who stop taking cholesterol drugs may be at an increased risk for developing Parkinson’s disease, according to research that appears in the July 24, 2013, online issue of Neurology®, the medical journal of the American Academy of Neurology. Previous studies on the relationship between cholesterol drugs called statins and the risk of Parkinson’s disease have had inconsistent results.

The current study involved 43,810 people in Taiwan who were taking statins and did not have Parkinson’s disease. Taiwan’s compulsory national health insurance program reimbursement policy requests that doctors stop prescribing statins once the patient’s cholesterol reaches the treatment goal, which is contrary to standard treatment in the United States.

“This policy allowed us to see whether there was any difference in the risk of Parkinson’s in people who stopped taking statins compared to the ones who kept taking them,” said study author Jou-Wei Lin, MD, PhD, of National Taiwan University in Taipei.

The study found a difference between two types of statins. The use of lipophilic, or fat-soluble, statins such as simvastatin and atorvastatin was associated with a reduced risk of Parkinson’s, while no such association was found for hydrophilic, or water-soluble, statins such as pravastatin and rosuvastatin.

Those who stopped taking the fat-soluble statins were 58 percent more likely to develop Parkinson’s disease than those who kept taking the drugs, an absolute risk of 2.65 cases per one million person-days. This result was consistent even after adjusting for other conditions such as diabetes and high blood pressure.

The study also looked at how many people taking the two types of statins developed Parkinson’s disease, compared to the number of person-days spent on the medication to come up with an incidence rate. A total of 25 people taking fat-soluble statins developed Parkinson’s from a total of nearly 15 million person-days on the drugs, for a rate of 1.68 cases per one million person-days on the drugs. For the water-soluble statins, 14 people developed Parkinson’s from nearly four million person-days on the drugs, for a rate of 3.52 cases per one million person-days on the drugs.

“The fat-soluble statins are better able to cross the blood-brain barrier than the water-soluble statins,” Lin said.

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The study was supported by the Taiwan Ministry of Education.

To learn more about Parkinson’s disease, please visit http://www.aan.com/patients.

The American Academy of Neurology, an association of more than 26,000 neurologists and neuroscience professionals, is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, brain injury, Parkinson’s disease and epilepsy.

For more information about the American Academy of Neurology, visit http://www.aan.com or find us on Facebook, Twitter, Google+ and YouTube.

Media Contacts: Rachel Seroka, rseroka@aan.com, (612) 928-6129 Michelle Uher, muher@aan.com, (612) 928-6120

Artificial Sweetener ( Mannitol ) a Potential Treatment for Parkinson’s Disease

Monday, June 17, 2013

TAU researcher says mannitol could prevent aggregation of toxic proteins in the brain

Mannitol, a sugar alcohol produced by fungi, bacteria, and algae, is a common component of sugar-free gum and candy. The sweetener is also used in the medical field — it’s approved by the FDA as a diuretic to flush out excess fluids and used during surgery as a substance that opens the blood/brain barrier to ease the passage of other drugs.

Now Profs. Ehud Gazit and Daniel Segal of Tel Aviv University’s Department of Molecular Microbiology and Biotechnology and the Sagol School of Neuroscience, along with their colleague Dr. Ronit Shaltiel-Karyo and PhD candidate Moran Frenkel-Pinter, have found that mannitol also prevents clumps of the protein α-synuclein from forming in the brain — a process that is characteristic of Parkinson’s disease.

These results, published in the Journal of Biological Chemistry and presented at the Drosophila Conference in Washington, DC in April, suggest that this artificial sweetener could be a novel therapy for the treatment of Parkinson’s and other neurodegenerative diseases. The research was funded by a grant from the Parkinson’s Disease Foundation and supported in part by the Lord Alliance Family Trust.

Seeing a significant difference

After identifying the structural characteristics that facilitate the development of clumps of α-synuclein, the researchers began to hunt for a compound that could inhibit the proteins’ ability to bind together. In the lab, they found that mannitol was among the most effective agents in preventing aggregation of the protein in test tubes. The benefit of this substance is that it is already approved for use in a variety of clinical interventions, Prof. Segal says.

Next, to test the capabilities of mannitol in the living brain, the researchers turned to transgenic fruit flies engineered to carry the human gene for α-synuclein. To study fly movement, they used a test called the “climbing assay,” in which the ability of flies to climb the walls of a test tube indicates their locomotive capability. In the initial experimental period, 72 percent of normal flies were able to climb up the test tube, compared to only 38 percent of the genetically-altered flies.

The researchers then added mannitol to the food of the genetically-altered flies for a period of 27 days and repeated the experiment. This time, 70 percent of the mutated flies could climb up the test tube. In addition, the researchers observed a 70 percent reduction in aggregates of α-synuclein in mutated flies that had been fed mannitol, compared to those that had not.

These findings were confirmed by a second study which measured the impact of mannitol on mice engineered to produce human α-synuclein, developed by Dr. Eliezer Masliah of the University of San Diego. After four months, the researchers found that the mice injected with mannitol also showed a dramatic reduction of α-synuclein in the brain.

Delivering therapeutic compounds to the brain

The researchers now plan to re-examine the structure of the mannitol compound and introduce modifications to optimize its effectiveness. Further experiments on animal models, including behavioral testing, whose disease development mimics more closely the development of Parkinson’s in humans is needed, Prof. Segal says.

For the time being, mannitol may be used in combination with other medications that have been developed to treat Parkinson’s but which have proven ineffective in breaking through the blood/brain barrier, says Prof. Segal. These medications may be able to “piggy-back” on mannitol’s ability to open this barrier into the brain.

Although the results look promising, it is still not advisable for Parkinson’s patients to begin ingesting mannitol in large quantities, Prof. Segal cautions. More testing must be done to determine dosages that would be both effective and safe

Common Food Supplement Fights Degenerative Brain Disorders : Phosphatidylserine

Common Food Supplement Fights Degenerative Brain Disorders Tuesday, May 21, 2013

Nutritional supplement delays advancement of Parkinson’s and Familial Dysautonomia, TAU researchers discover

Widely available in pharmacies and health stores, phosphatidylserine is a natural food supplement produced from beef, oysters, and soy. Proven to improve cognition and slow memory loss, it’s a popular treatment for older people experiencing memory impairment. Now a team headed by Prof. Gil Ast and Dr. Ron Bochner of Tel Aviv University‘s Department of Human Molecular Genetics has discovered that the same supplement improves the functioning of genes involved in degenerative brain disorders, including Parkinson’s disease and Familial Dysautonomia (FD).

In FD, a rare genetic disorder that impacts the nervous system and appears almost exclusively in the Ashkenazi Jewish population, a genetic mutation prevents the brain from manufacturing healthy IKAP proteins — which likely have a hand in cell migration and aiding connections between nerves — leading to the early degeneration of neurons. When the supplement was applied to cells taken from FD patients, the gene function improved and an elevation in the level of IKAP protein was observed, reports Prof. Ast. These results were replicated in a second experiment which involved administering the supplement orally to mouse populations with FD.

The findings, which have been published in the journal Human Molecular Genetics, are very encouraging, says Prof. Ast. “That we see such an effect on the brain — the most important organ in relation to this disease — shows that the supplement can pass through the blood-brain barrier even when administered orally, and accumulate in sufficient amounts in the brain.”

Slowing the death of nerve cells

Already approved for use as a supplement by the FDA, phosphatidylserine contains a molecule essential for transmitting signals between nerve cells in the brain. Prof. Ast and his fellow researchers decided to test whether the same chemical, which is naturally synthesized in the body and known to boost memory capability, could impact the genetic mutation which leads to FD.

Researchers applied a supplement derived from oysters, provided by the Israeli company Enzymotec, to cells collected from FD patients. Noticing a robust effect on the gene, including a jump in the production of healthy IKAP proteins, they then tested the same supplement on mouse models of FD, engineered with the same genetic mutation that causes the disease in humans.

The mice received the supplement orally, every two days for a period of three months. Researchers then conducted extensive genetic testing to assess the results of the treatment. “We found a significant increase of the protein in all the tissues of the body,” reports Prof. Ast, including an eight-fold increase in the liver and 1.5-fold increase in the brain. “While the food supplement does not manufacture new nerve cells, it probably delays the death of existing ones,” he adds.

Therapeutic potential for Parkinson’s

That the supplement is able to improve conditions in the brain, even when given orally, is a significant finding, notes Prof. Ast. Most medications enter the body through the blood stream, but are incapable of breaking through the barrier between the blood and the brain.

In addition, the researchers say the supplement’s positive effects extend beyond the production of IKAP. Not only did phosphatidylserine impact the gene associated with FD, but it also altered the level of a total of 2400 other genes — hundreds of which have been connected to Parkinson’s disease in previous studies.

The researchers believe that the supplement may have a beneficial impact on a number of degenerative diseases of the brain, concludes Prof. Ast, including a major potential for the development of new medications which would help tens of millions of people worldwide suffering from these devastating diseases

Could eating peppers prevent Parkinson’s?

Contact: Dawn Peters sciencenewsroom@wiley.com 781-388-8408 Wiley

Dietary nicotine may hold protective key

New research reveals that Solanaceae—a flowering plant family with some species producing foods that are edible sources of nicotine—may provide a protective effect against Parkinson’s disease. The study appearing today in Annals of Neurology, a journal of the American Neurological Association and Child Neurology Society, suggests that eating foods that contain even a small amount of nicotine, such as peppers and tomatoes, may reduce risk of developing Parkinson’s.

Parkinson’s disease is a movement disorder caused by a loss of brain cells that produce dopamine. Symptoms include facial, hand, arm, and leg tremors, stiffness in the limbs, loss of balance, and slower overall movement. Nearly one million Americans have Parkinson’s, with 60,000 new cases diagnosed in the U.S. each year, and up to ten million individuals worldwide live with this disease according to the Parkinson’s Disease Foundation. Currently, there is no cure for Parkinson’s, but symptoms are treated with medications and procedures such as deep brain stimulation.

Previous studies have found that cigarette smoking and other forms of tobacco, also a Solanaceae plant, reduced relative risk of Parkinson’s disease. However, experts have not confirmed if nicotine or other components in tobacco provide a protective effect, or if people who develop Parkinson’s disease are simply less apt to use tobacco because of differences in the brain that occur early in the disease process, long before diagnosis.

For the present population-based study Dr. Susan Searles Nielsen and colleagues from the University of Washington in Seattle recruited 490 patients newly diagnosed with Parkinson’s disease at the university’s Neurology Clinic or a regional health maintenance organization, Group Health Cooperative. Another 644 unrelated individuals without neurological conditions were used as controls. Questionnaires were used to assess participants’ lifetime diets and tobacco use, which researchers defined as ever smoking more than 100 cigarettes or regularly using cigars, pipes or smokeless tobacco.

Vegetable consumption in general did not affect Parkinson’s disease risk, but as consumption of edible Solanaceae increased, Parkinson’s disease risk decreased, with peppers displaying the strongest association. Researchers noted that the apparent protection from Parkinson’s occurred mainly in men and women with little or no prior use of tobacco, which contains much more nicotine than the foods studied.

“Our study is the first to investigate dietary nicotine and risk of developing Parkinson’s disease,” said Dr. Searles Nielsen. “Similar to the many studies that indicate tobacco use might reduce risk of Parkinson’s, our findings also suggest a protective effect from nicotine, or perhaps a similar but less toxic chemical in peppers and tobacco.” The authors recommend further studies to confirm and extend their findings, which could lead to possible interventions that prevent Parkinson’s disease.

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This study is published in Annals of Neurology. Media wishing to receive a PDF of this article may contact sciencenewsroom@wiley.com.

Full citation: “Nicotine from Edible Solanaceae and Risk of Parkinson Disease.” Susan Searles Nielsen, Gary M. Franklin, W.T. Longstreth Jr, Phillip D. Swanson and Harvey Checkoway. Annals of Neurology; Published May 9, 2013 (DOI:10.1002/ana.23884).

URL Upon Publication: http://doi.wiley.com/10.1002/ana.23884

Author Contact: To arrange an interview with Dr. Susan Searles Nielsen, please contact Leila Gray with the University of Washington Health Sciences News Office at +1 206-685-0381 or at leilag@uw.edu.

About the Journal

Annals of Neurology, the official journal of the American Neurological Association and the Child Neurology Society, publishes articles of broad interest with potential for high impact in understanding the mechanisms and treatment of diseases of the human nervous system. All areas of clinical and basic neuroscience, including new technologies, cellular and molecular neurobiology, population sciences, and studies of behavior, addiction, and psychiatric diseases are of interest to the journal. The journal is published by Wiley on behalf of the American Neurological Association and Child Neurology Society. For more information, please visit http://onlinelibrary.wiley.com/journal/10.1002/ana.

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Molecular link between diabetes and schizophrenia connects food and mood

2010 study posted for filing

 

Contact: Leigh MacMillan leigh.macmillan@vanderbilt.edu 615-322-4747 Vanderbilt University Medical Center

Defects in insulin function – which occur in diabetes and obesity – could directly contribute to psychiatric disorders like schizophrenia.

Vanderbilt University Medical Center investigators have discovered a molecular link between impaired insulin signaling in the brain and schizophrenia-like behaviors in mice. The findings, reported June 8 in PLoS Biology, offer a new perspective on the psychiatric and cognitive disorders that affect patients with diabetes and suggest new strategies for treating these conditions.

“We know that people with diabetes have an increased incidence of mood and other psychiatric disorders,” said endocrinologist Kevin Niswender, M.D., Ph.D. “And we think that those co-morbidities might explain why some patients have trouble taking care of their diabetes.”

“Something goes wrong in the brain because insulin isn’t signaling the way that it normally does,” said neurobiologist Aurelio Galli, Ph.D.

Galli’s group was among the first to show that insulin – the hormone that governs glucose metabolism in the body – also regulates the brain’s supply of dopamine – a neurotransmitter with roles in motor activity, attention and reward. Disrupted dopamine signaling has been implicated in brain disorders including depression, Parkinson’s disease, schizophrenia and attention-deficit hyperactivity disorder.

Now, Galli, Niswender, and colleagues have pieced together the molecular pathway between perturbed insulin signaling in the brain and dopamine dysfunction leading to schizophrenia-like behaviors.

The researchers developed mice with an insulin-signaling defect only in neurons (they impaired the function of the protein Akt, which transmits insulin’s signal inside cells). They found that the mice have behavioral abnormalities similar to those frequently seen in patients with schizophrenia.

They also showed how defects in insulin signaling disrupt neurotransmitter levels in the brain – the mice have reduced dopamine and elevated norepinephrine in the prefrontal cortex, an important area for cognitive processes. These changes resulted from elevated levels of the transporter protein (NET) that removes norepinephrine and dopamine from the synaptic space between neurons.

“We believe the excess NET is sucking away all of the dopamine and converting it to norepinephrine, creating this situation of hypodopaminergia (low levels of dopamine) in the cortex,” Galli explained. Low dopamine function in the cortex is thought to contribute to the cognitive deficits and negative symptoms – depression, social withdrawal – associated with schizophrenia.

By treating the mice with NET inhibitors (drugs that block NET activity), the investigators were able to restore normal cortical dopamine levels and behaviors. Clinical trials of NET inhibitors in patients with schizophrenia are already under way, Galli said, and these new data provide mechanistic support for this approach.

The findings also provide a molecular basis for interpreting previous reports of Akt deficiencies in patients with schizophrenia, as revealed by post-mortem, imaging and genetic association studies.

Galli and Niswender suggest that the insulin to Akt signaling pathway is critical for “fine-tuning” the function of monoamine neurotransmitters – dopamine, norepinephrine and serotonin – and that it can be impaired in many different ways.

“Dysregulation of this pathway – because of type 1 diabetes, because of a high-fat diet, because of drugs of abuse, because of genetic variations – may put a person on the road to neuropsychiatric disorders,” Galli said.

Understanding the molecular link between insulin action and dopamine balance – the connection between food and mood – offers the potential for novel therapeutic approaches, the researchers said. The mouse model described in the current studies may be useful for testing schizophrenia and cognition-enhancing treatments.

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Michael Siuta and Sabrina Robertson are the lead authors of the study. Niswender is an assistant professor of Medicine and Molecular Physiology & Biophysics; Galli is a professor of Molecular Physiology & Biophysics.

The National Institutes of Health and the Vanderbilt University Silvio O. Conte Center for Neuroscience Research supported the research.

Head injury + pesticide exposure = Triple the risk of Parkinson’s disease

Contact: Rachel Seroka
rseroka@aan.com
612-928-6129
American Academy of Neurology

MINNEAPOLIS – A new study shows that people who have had a head injury and have lived or worked near areas where the pesticide paraquat was used may be three times more likely to develop Parkinson’s disease. The study is published in the November 13, 2012, print issue of Neurology®, the medical journal of the American Academy of Neurology. Paraquat is a herbicide commonly used on crops to control weeds. It can be deadly to humans and animals.

“While each of these two factors is associated with an increased risk of Parkinson’s on their own, the combination is associated with greater risk than just adding the two factors together,” said study author Beate Ritz, MD, PhD, of UCLA’s Fielding School of Public Health. “This study suggests that the physiological process that is triggered by a head injury may increase brain cells’ vulnerability to attacks from pesticides that can be toxic to the brain or the other way around, for example, chronic low dose exposure to pesticides may increase the risk of Parkinson’s after a head injury.”

The study involved 357 people with Parkinson’s disease and 754 people without the disease, all of whom lived in an agricultural area in central California. The participants reported any head injuries they had ever received with a loss of consciousness for more than five minutes.

The researchers determined participants’ exposure to the weed killer based on a 500-meter area around their home and work addresses, using a geographic information system (GIS) that combined data on paraquat use collected by the state of California’s Pesticide Use Reporting system with land use maps.

People with Parkinson’s disease were twice as likely to have had a head injury with loss of consciousness for more than five minutes as people who did not have the disease. Of the 357 people with Parkinson’s disease, 42, or 12 percent, reported ever having had such a head injury, compared to 50 of the 754 people without the disease, or 7 percent.

People with Parkinson’s disease were 36 percent more likely to have exposure to paraquat than those who did not have the disease. Of those with Parkinson’s, 169 had exposure to the weed killer, or 47 percent, compared to 291 of those without the disease, or 39 percent.

 

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The study was supported by the National Institute of Environmental Health Science, National Institute of Neurological Disorders and Stroke, National Institutes of Health and American Parkinson Disease Association.

To learn more about Parkinson’s disease, visit http://www.aan.com/patients.

The American Academy of Neurology, an association of more than 25,000 neurologists and neuroscience professionals, is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, brain injury, Parkinson’s disease and epilepsy. For more information about the American Academy of Neurology, visit http://www.aan.com or find us on Facebook, Twitter, Google+ and YouTube.

Media Contacts:

Rachel Seroka, rseroka@aan.com, (612) 928-6129

Angela Babb, APR, ababb@aan.com, (612) 928-6102

On-the-job pesticide exposure associated with Parkinson’s disease

Contact: Jonathan Friedman jfriedman@thepi.org 408-542-5606 JAMA and Archives Journals

Individuals whose occupation involves contact with pesticides appear to have an increased risk of having Parkinson’s disease, according to a report in the September issue of Archives of Neurology, one of the JAMA/Archives journals.

The development of Parkinson’s disease related to chemical exposure was identified in the late 20th century, according to background information in the article. Since then, occupations such as farming, teaching and welding have all been proposed to increase the risk of Parkinson’s disease. However, associations have been inconsistent and few previous studies have evaluated the direct relationship between occupational chemical exposure and disease risk.

Caroline M. Tanner, M.D., Ph.D., of the Parkinson’s Institute, Sunnyvale, Calif., and colleagues studied 519 individuals with Parkinson’s disease and 511 controls who were the same age and sex and lived in the same location. Participants were surveyed about their occupational history and exposure to toxins, including solvents and pesticides.

Working in agriculture, education, health care or welding was not associated with Parkinson’s disease, nor was any other specific occupation studied after adjustment for other factors.

Among the patients with Parkinson’s disease, 44 (8.5 percent) reported pesticide exposure compared with 27 (5.3 percent) of controls, such that occupational pesticide exposure was associated with an increased risk of the disease. “Growing evidence suggests a causal association between pesticide use and parkinsonism. However, the term ‘pesticide’ is broad and includes chemicals with varied mechanisms,” the authors write. “Because few investigations have identified specific pesticides, we studied eight pesticides with high neurotoxic plausibility based on laboratory findings. Use of these pesticides was associated with higher risk of parkinsonism, more than double that in those not exposed.”

Three individual compounds—an organochloride (2,4-dichlorophenoxyacetic acid), an herbicide (paraquat) and an insecticide (permethrin)—were associated with a more than three-fold increased risk of Parkinson’s disease. All three have been shown to have effects on dopaminergic neurons—affected by Parkinson’s disease—in the laboratory.

“This convergence of epidemiologic and laboratory data from experimental models of Parkinson’s disease lends credence to a causative role of certain pesticides in the neurodegenerative process,” the authors conclude. “Other pesticide exposures such as hobby gardening, residential exposure, wearing treated garments or dietary intake were not assessed. Because these exposures may affect many more subjects, future attention is warranted.”

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(Arch Neurol. 2009;66[9]:1106-1113. Available pre-embargo to the media at www.jamamedia.org.)

Editor’s Note: This study was supported by an unrestricted grant from a group of current and former manufacturers of welding consumables awarded to The Parkinson’s Institute. Co-author Dr. Hauser has received fees for providing expert testimony in cases related to Parkinson’s disease in welders. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Challenging Parkinson’s dogma: May be more to due with the Loss of GABA than Dopamine

Contact: David Cameron david_cameron@hms.harvard.edu 617-432-0441 Harvard Medical School

Scientists may have discovered why the standard treatment for Parkinson’s disease is often effective for only a limited period of time. Their research could lead to a better understanding of many brain disorders, from drug addiction to depression, that share certain signaling molecules involved in modulating brain activity.

A team led by Bernardo Sabatini, Takeda Professor of Neurobiology at Harvard Medical School, used mouse models to study dopamine neurons in the striatum, a region of the brain involved in both movement and learning. In people, these neurons release dopamine, a neurotransmitter that allows us to walk, speak and even type on a keyboard. When those cells die, as they do in Parkinson’s patients, so does the ability to easily initiate movement. Current Parkinson’s drugs are precursors of dopamine that are then converted into dopamine by cells in the brain.

The flip side of dopamine dearth is dopamine hyperactivity. Heroin, cocaine and amphetamines rev up or mimic dopamine neurons, ultimately reinforcing the learned reward of drug-taking. Other conditions such as obsessive-compulsive disorder, Tourette syndrome and even schizophrenia may also be related to the misregulation of dopamine.

In the October 11 issue of Nature, Sabatini and co-authors Nicolas Tritsch and Jun Ding reported that midbrain dopamine neurons release not only dopamine but also another neurotransmitter called GABA, which lowers neuronal activity. The previously unsuspected presence of GABA could explain why restoring only dopamine could cause initial improvements in Parkinson’s patients to eventually wane. And if GABA is made by the same cells that produce other neurotransmitters, such as depression-linked serotonin, similar single-focus treatments could be less successful for the same reason.

“If what we found in the mouse applies to the human, then dopamine’s only half the story,” said Sabatini.

The surprising GABA story began in the Sabatini lab with a series of experiments designed to see what happens when cells release dopamine. The scientists used optogenetics, a powerful technique that relies on genetic manipulation to selectively sensitize cells to light. In laboratory dishes, researchers tested brain tissue from mice engineered to show activity in dopamine neurons. Typically in such experiments, other neurotransmitters would be blocked in order to highlight dopamine, but Tritsch, a postdoctoral fellow in the Sabatini lab, decided instead to keep the cell in as natural a state as possible.

When Tritsch activated the dopamine neurons and examined their effects on striatal neurons, he naturally expected to observe the effects of dopamine release. Instead, he saw rapid inhibition of the striatal neurons, making it clear that another neurotransmitter – which turned out to be the quick-acting GABA – was at work.  This was so unusual that the team launched a series of experiments to confirm that GABA was being released directly by these dopamine neurons.

A standard way to detect GABA is to look for vesicular GABA transporter, or VGAT, a protein that packages and carries GABA into neurotransmitter vesicles. The scientists silenced the gene that makes VGAT in mice and found that the dopamine neurons released GABA even in the absence of VGAT.

The researchers then tested other transporters, zeroing in on one that ferries dopamine and a variety of other neurotransmitters. For reasons they don’t yet understand, this protein – the vesicular monoamine transporter – also shuttles GABA.

“What makes this important now is that every manipulation that has targeted dopamine by targeting the vesicular monoamine transporter has altered GABA as well. And nobody’s paid any attention to it,” said Sabatini. “Every Parkinsonian model that we have in which we’ve lost dopamine has actually lost GABA, too. So we really have to go back now and think: Which of these effects are due to loss of GABA and which are due to loss of dopamine?”

Anatol Kreitzer, an assistant investigator at the Gladstone Institute of Neurological Disease in San Francisco, who was not involved in the research, called the findings remarkable.

“It was totally unexpected,” said Kreitzer, who is also an assistant professor of physiology and neurology at the University of California, San Francisco. “At the molecular level, nobody really expected dopamine neurons to be releasing significant amounts of GABA. At the functional level, it’s surprising that this major modulator of plasticity in the brain, which is so critical for Parkinson’s, for learning and rewards, and for other psychiatric illnesses, can also release GABA. That raises a question as to what role GABA has.”

GABA can very quickly change the electrical state of cells, inhibiting their activity by making them less excitable. Sabatini wonders if the loss of GABA in dopamine neurons could explain why hyperactivity is sometimes seen after chronic loss of these neurons.

The next challenge will be to explore whether other neurons that express the vesicular monoamine transporter also release GABA in addition to neurotransmitters such as serotonin and noradrenaline.

“These findings highlight how little we actually know about the most basic features of cell identity in the brain,” said Sabatini.

Tritsch said what started out as a straightforward project to understand dopamine quickly changed direction, with lots of starts and stops on the way to some exciting new findings.

“It can be nice to come up with a hypothesis, test it, verify it, and have everything fall into place,” he said. “But biology rarely works that way.”

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This research was funded by a Nancy Lurie Marks Family Foundation postdoctoral fellowship and by grants from the National Institutes of Health (NS046579 and 4R00NS075136).

Pesticide levels in blood linked to Parkinson’s disease, UT Southwestern researchers find

2009 study posted for filing

Contact: Aline McKenzie
aline.mckenzie@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center

DALLAS – July 13, 2009 – People with Parkinson’s disease have significantly higher blood levels of a particular pesticide than healthy people or those with Alzheimer’s disease, researchers at UT Southwestern Medical Center have found.

In a study appearing in the July issue of Archives of Neurology, researchers found the pesticide beta-HCH (hexachlorocyclohexane) in 76 percent of people with Parkinson’s, compared with 40 percent of healthy controls and 30 percent of those with Alzheimer’s.

The finding might provide the basis for a beta-HCH blood test to identify individuals at risk for developing Parkinson’s disease. The results also point the way to more research on environmental causes of Parkinson’s.

“There’s been a link between pesticide use and Parkinson’s disease for a long time, but never a specific pesticide,” said Dr. Dwight German, professor of psychiatry at UT Southwestern and a senior author of the paper. “This is particularly important because the disease is not diagnosed until after significant nerve damage has occurred. A test for this risk factor might allow for early detection and protective treatment.”

About 1 million people in the U.S. have Parkinson’s, a number expected to rise as the population ages. The disease occurs when brain cells in particular regions die, causing tremors, cognitive problems and a host of other symptoms.

The study involved 113 participants, ages 50 to 89. Fifty had Parkinson’s, 43 were healthy and 20 had Alzheimer’s. The researchers tested the subjects’ blood for 15 pesticides known as organochlorines.

These pesticides, which include the well-known DDT (dichlorodiphenyltrichloroethane), were widely used in the U.S. from the 1950s to the 1970s but are more tightly regulated now. They persist in the environment for years without breaking down. In the body, they dissolve in fats and are known to attack the type of brain nerves that die in Parkinson’s disease, the researchers said.

“Much higher levels of the beta-HCH were in the air, water and food chain when the Parkinson’s patients were in their 20s and30s,” Dr. German said. “Also, the half-life of the pesticide is seven to eight years, so it stays in the body for a long time.”

Parkinson’s disease is more common among rural men than other demographic groups, but it is not a matter of a single factor causing the devastating disease, Dr. German said.

“Some people with Parkinson’s might have the disease because of exposure to environmental pesticides, but there are also genes known to play a role in the condition,” Dr. German said.

Although the current study points to an interesting link between the pesticide beta-HCH and Parkinson’s, there could be other pesticides involved with the disease, he said.

For example, the pesticide lindane often contains beta-HCH, but lindane breaks down faster. Beta-HCH might simply be a sign that someone was exposed to lindane, with lindane actually causing the damage to the brain, the researchers said.

In future research, Dr. German hopes to test patients from a wider geographical area and to measure pesticide levels in post-mortem brains. He and his team also are collecting blood samples from both patients with Parkinson’s and their spouses to see if a genetic difference might be making the one with Parkinson’s more susceptible to pesticides than the other.

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Other UT Southwestern researchers involved in the study were Dr. Padraig O’Suilleabhain, associate professor of neurology; Dr. Ramón Diaz-Arrastía, professor of neurology; and Dr. Joan Reisch, professor of clinical sciences.

Researchers from the Robert Wood Johnson Medical School, including lead author Dr. Jason Richardson, and the Environmental and Occupational Health Sciences Institute in New Jersey also participated in the study.

The study was funded by the National Institute of Environmental Health Sciences, the National Institute on Aging, the Dallas Area Parkinsonism Society, Rowe & Co. Inc., the Dallas Foundation and the Michael J. Fox Foundation for Parkinson’s Research.

Visit www.utsouthwestern.org/neurosciences to learn more about UT Southwestern’s clinical services in neurosciences, including psychiatry.

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Researchers find possible environmental causes for Alzheimer’s, diabetes : nitrates

2009 study posted for filing

Contact: Nancy Cawley Jean njean@lifespan.org Lifespan

Call for reducing nitrate levels in fertilizer and water, detoxifying food and water

Providence, RI – A new study by researchers at Rhode Island Hospital have found a substantial link between increased levels of nitrates in our environment and food with increased deaths from diseases, including Alzheimer’s, diabetes mellitus and Parkinson’s. The study was published in the Journal of Alzheimer’s Disease (Volume 17:3 July 2009).

Led by Suzanne de la Monte, MD, MPH, of Rhode Island Hospital, researchers studied the trends in mortality rates due to diseases that are associated with aging, such as diabetes, Alzheimer’s, Parkinson’s, diabetes and cerebrovascular disease, as well as HIV. They found strong parallels between age adjusted increases in death rate from Alzheimer’s, Parkinson’s, and diabetes and the progressive increases in human exposure to nitrates, nitrites and nitrosamines through processed and preserved foods as well as fertilizers. Other diseases including HIV-AIDS, cerebrovascular disease, and leukemia did not exhibit those trends. De la Monte and the authors propose that the increase in exposure plays a critical role in the cause, development and effects of the pandemic of these insulin-resistant diseases.

De la Monte, who is also a professor of pathology and lab medicine at The Warren Alpert Medical School of Brown University, says, “We have become a ‘nitrosamine generation.’ In essence, we have moved to a diet that is rich in amines and nitrates, which lead to increased nitrosamine production. We receive increased exposure through the abundant use of nitrate-containing fertilizers for agriculture.” She continues, “Not only do we consume them in processed foods, but they get into our food supply by leeching from the soil and contaminating water supplies used for crop irrigation, food processing and drinking.”

Nitrites and nitrates belong to a class of chemical compounds that have been found to be harmful to humans and animals. More than 90 percent of these compounds that have been tested have been determined to be carcinogenic in various organs. They are found in many food products, including fried bacon, cured meats and cheese products as well as beer and water. Exposure also occurs through manufacturing and processing of rubber and latex products, as well as fertilizers, pesticides and cosmetics.

Nitrosamines are formed by a chemical reaction between nitrites or other proteins. Sodium nitrite is deliberately added to meat and fish to prevent toxin production; it is also used to preserve, color and flavor meats. Ground beef, cured meats and bacon in particular contain abundant amounts of amines due to their high protein content. Because of the significant levels of added nitrates and nitrites, nitrosamines are nearly always detectable in these foods. Nitrosamines are also easily generated under strong acid conditions, such as in the stomach, or at high temperatures associated with frying or flame broiling. Reducing sodium nitrite content reduces nitrosamine formation in foods.

Nitrosamines basically become highly reactive at the cellular level, which then alters gene expression and causes DNA damage. The researchers note that the role of nitrosamines has been well-studied, and their role as a carcinogen has been fully documented. The investigators propose that the cellular alterations that occur as a result of nitrosamine exposure are fundamentally similar to those that occur with aging, as well as Alzheimer’s, Parkinson’s and Type 2 diabetes mellitus.

De la Monte comments, “All of these diseases are associated with increased insulin resistance and DNA damage. Their prevalence rates have all increased radically over the past several decades and show no sign of plateau. Because there has been a relatively short time interval associated with the dramatic shift in disease incidence and prevalence rates, we believe this is due to exposure-related rather than genetic etiologies.”

The researchers recognize that an increase in death rates is anticipated in higher age groups. Yet when the researchers compared mortality from Parkinson’s and Alzheimer’s disease among 75 to 84 year olds from 1968 to 2005, the death rates increased much more dramatically than for cerebrovascular and cardiovascular disease, which are also aging-associated. For example, in Alzheimer’s patients, the death rate increased 150-fold, from 0 deaths to more than 150 deaths per 100,000. Parkinson’s disease death rates also increased across all age groups. However, mortality rates from cerebrovascular disease in the same age group declined, even though this is a disease associated with aging as well.

De la Monte notes, “Because of the similar trending in nearly all age groups within each disease category, this indicates that these overall trends are not due to an aging population. This relatively short time interval for such dramatic increases in death rates associated with these diseases is more consistent with exposure-related causes rather than genetic changes.” She also comments, “Moreover, the strikingly higher and climbing mortality rates in older age brackets suggest that aging and/or longer durations of exposure have greater impacts on progression and severity of these diseases.”

The researchers graphed and analyzed mortality rates, and compared them with increasing age for each disease. They then studied United States population growth, annual use and consumption of nitrite-containing fertilizers, annual sales at popular fast food chains, and sales for a major meat processing company, as well as consumption of grain and consumption of watermelon and cantaloupe (the melons were used as a control since they are not typically associated with nitrate or nitrite exposure).

The findings indicate that while nitrogen-containing fertilizer consumption increased by 230 percent between 1955 and 2005, its usage doubled between 1960 and 1980, which just precedes the insulin-resistant epidemics the researchers found. They also found that sales from the fast food chain and the meat processing company increased more than 8-fold from 1970 to 2005, and grain consumption increased 5-fold.

The authors state that the time course of the increased prevalence rates of Alzheimer’s, Parkinson’s and diabetes cannot be explained on the basis of gene mutations. They instead mirror the classical trends of exposure-related disease. Because nitrosamines produce biochemical changes within cells and tissues, it is conceivable that chronic exposure to low levels of nitrites and nitrosamines through processed foods, water and fertilizers is responsible for the current epidemics of these diseases and the increasing mortality rates associated with them.

De la Monte states, “If this hypothesis is correct, potential solutions include eliminating the use of nitrites and nitrates in food processing, preservation and agriculture; taking steps to prevent the formation of nitrosamines and employing safe and effective measures to detoxify food and water before human consumption.”

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Other researchers involved in the study with de la Monte include Alexander Neusner, Jennifer Chu and Margot Lawton, from the departments of pathology, neurology and medicine at Rhode Island Hospital and The Warren Alpert Medical School of Brown University.

The study was funded through grants from the National Institutes of Health. Two subsequent papers have been accepted for publication in the near future that demonstrate experimentally that low levels of nitrosamine exposure cause neurodegeneration, NASH and diabetes.

De la Monte, Suzanne M., Alexander Neusner, Jennifer Chu and Margot Lawton. “Epidemilogical Trends Strongly Suggest Exposures as Etiologic Agents in the Pathogenesis of Sporadic Alzheimer’s Disease, Diabetes Mellitus, and Non-Alcoholic Steatohepatitis.” Journal of Alzheimer’s Disease, 17:3 (July 2009) pp 519-529.

The Journal of Alzheimer’s Disease (http://www.j-alz.com) is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer’s disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Groundbreaking research that has appeared in the journal includes novel therapeutic targets, mechanisms of disease and clinical trial outcomes. The Journal of Alzheimer’s Disease has an Impact Factor of 5.101 according to Thomson Reuters’ 2008 Journal Citation Reports. The Journal is published by IOS Press (http://www.iospress.nl).

Founded in 1863, Rhode Island Hospital (www.rhodeislandhospital.org) in Providence, RI, is a private, not-for-profit hospital and is the largest teaching hospital of the Warren Alpert Medical School of Brown University. A major trauma center for southeastern New England, the hospital is dedicated to being on the cutting edge of medicine and research. Many of its physicians are recognized as leaders in their respective fields of cancer, cardiology, diabetes, emergency medicine and trauma, neuroscience, orthopedics, pediatrics, radiation oncology and surgery. Rhode Island Hospital receives nearly $50 million each year in external research funding. It is home to Hasbro Children’s Hospital, the state’s only facility dedicated to pediatric care, which is ranked among the top 30 children’s hospitals in the country by Parents magazine. Rhode Island Hospital is a founding member of the Lifespan health system.

Association Found Between Parkinson’s Disease and Pesticide Exposure in French Farm Workers: pesticide exposure may lead to neurodegeneration

2009 study posted for filing

Paris, France – June 04, 2009 – The cause of Parkinson’s disease (PD), the second most frequent neurodegenerative disease after Alzheimer’s disease, is unknown, but in most cases it is believed to involve a combination of environmental risk factors and genetic susceptibility. Laboratory studies in rats have shown that injecting the insecticide rotenone leads to an animal model of PD and several epidemiological studies have shown an association between pesticides and PD, but most have not identified specific pesticides or studied the amount of exposure relating to the association.

A new epidemiological study involving the exposure of French farm workers to pesticides found that professional exposure is associated with PD, especially for organochlorine insecticides. The study is published in Annals of Neurology, the official journal of the American Neurological Association.

Led by Alexis Elbaz M.D., Ph.D., of Inserm, the national French institute for health research in Paris, and University Pierre et Marie Curie (UPMC, Paris 6), the study involved individuals affiliated with the French health insurance organization for agricultural workers who were frequently exposed to pesticides in the course of their work. Occupational health physicians constructed a detailed lifetime exposure history to pesticides by interviewing participants, visiting farms, and collecting a large amount of data on pesticide exposure. These included farm size, type of crops, animal breeding, which pesticides were used, time period of use, frequency and duration of exposure per year, and spraying method.

The study found that PD patients had been exposed to pesticides through their work more frequently and for a greater number of years/hours than those without PD. Among the three main classes of pesticides (insecticides, herbicides, fungicides), researchers found the largest difference for insecticides: men who had used insecticides had a two-fold increase in the risk of PD.

“Our findings support the hypothesis that environmental risk factors such as professional pesticide exposure may lead to neurodegeneration,” notes Dr. Elbaz.

The study highlights the need to educate workers applying pesticides as to how these products should be used and the importance of promoting and encouraging the use of protective devices. In addition to the significance of the study for those with a high level of exposure to pesticides, it also raises the question about the role of lower-level environmental exposure through air, water and food, and additional studies are needed to address this question.

21st Health Research Report 26 DEC 2007 – Reconstruction

21st Health Research Report 26 DEC 2007 – Reconstruction (link below)

In This issue:

1. Elective Caesareans carry increased risk of breathing problems
2. Cholesterol-lowering drugs and the risk of hemorrhagic stroke
3. Turkish health workers condone wife beating
4. New clinical data shows chromium picolinate improves cognitive function
5. Green tea may protect brain cells against Parkinson’s disease
6. Vitamin B12 function may be diminished by excessive folate
7. Does treating worms in people with HIV slow progression to AIDS?
8. Walking and moderate exercise help prevent dementia
9. Breath test can discriminate between a bacterial overgrowth and IBS
10. Why don’t we get cancer all the time?
11. Why exertion leads to exhaustion
12. Why fish oil is good for you
 
http://healthresearchreport.me/2007/12/26/21st-health-research-report-26-dec-2007-reconstruction/

Green tea may protect brain cells against Parkinson’s disease

Philadelphia, PA, December 13, 2007 – Does the consumption of green tea, widely touted to have beneficial effects on health, also protect brain cells” Authors of a new study being published in the December 15th issue of Biological Psychiatry share new data that indicates this may be the case. The authors investigated the effects of green tea polyphenols, a group of naturally occurring chemical substances found in plants that have antioxidant properties, in an animal model of Parkinson’s disease.

Parkinson’s disease is a progressive, degenerative disorder of the central nervous system, resulting from the loss of dopamine-producing brain cells, and there is presently no cure. According to Dr. Baolu Zhao, corresponding and senior author on this article, current treatments for Parkinson’s are associated with serious and important side effects. Their previous research has indicated that green tea possesses neuroprotective effects, leading Guo and colleagues to examine its effects specifically in Parkinson’s. The authors discovered that green tea polyphenols protect dopamine neurons that increases with the amount consumed. They also show that this protective effect is mediated by inhibition of the ROS-NO pathway, a pathway that may contribute to cell death in Parkinson’s.

Dr. Zhao’s hope is that eventually “green tea polyphenols may be developed into a safe and easily administrable drug for Parkinson’s disease.” Dr. Krystal agrees, that “if green tea consumption can be shown to have meaningful neuroprotective actions in patients, this would be an extremely important advance.”

*Reposted for Filing

Study of insecticide neurotoxicity yields clues to onset of Parkinson’s Disease, permethrin

BLACKSBURG, Va., March 24, 2003 — A grant from the U.S. Army has led Virginia Tech researchers to discover that exposure to some insecticides may cause a cascade of chemical events in the brain that could lead to Parkinson’s Disease.

Jeffrey R. Bloomquist, a neurotoxicologist and associate professor in the university’s Department of Entomology, will describe his findings as part of the International Award for Research in Agrochemicals, a symposium honoring Robert M. Hollingworth, at the annual meeting of the American Chemical Society in New Orleans this week.

“We found low-level exposures set in motion a process with an early onset that develops slowly and is persistent,” Bloomquist said. “More surprising is that high-level exposures resulted in few immediate effects that we could observe, but in the longer term there was a delayed effect.”

The Virginia Tech researchers studied the levels of dopamine, dopamine transporter protein expression, and the levels of a synaptic protein (alpha-synuclein) in mice exposed to various doses of the insecticide permethrin. The increase in dopamine uptake indicated the mouse’s system was reacting to a neurochemical insult caused by the presence of the insecticide. The slow response to high levels of exposure to pesticides is caused, Bloomquist thinks, by the system being overloaded and only after a period of a few weeks is it capable of responding to the insult in the same way as low doses.

In some individuals, dopamine-producing neurons may be challenged by genetic factors or by previous exposure to other neurotoxins. For individuals with a genetic predisposition, exposure to permethrin may trigger chemical events in the brain that result in an increased risk for damage to the area of the brain that is selectively damaged in Parkinson’s disease.

The loss of motor skills, resulting in symptoms such as muscle rigidity, shuffling gait, and a rhythmic tremor, has been linked to the loss of dopamine production in the brain. That loss of dopamine is the major neurochemical expression of Parkinson’s Disease.

“Our studies have documented low-dose effects of permethrin, doses below one-one thousandth of a lethal dose for a mouse, with effects on those brain pathways involved in Parkinson’s Disease,” he said. “We have found effects consistent with a pre-parkinsonsian condition, but not yet full-blown parkinsonism.”

Bloomquist also found permethrin exposure resulted in an overproduction of the protein alpha-synuclein at low doses. The accumulation of the protein is a major component of the formation of the Lewy bodies, fibrous tangles observed in the brains of patients with Parkinson’s Disease.

The studies so far have concentrated on two-week exposures in mice. Bloomquist hopes to continue the work, looking at longer-term exposure. He is also studying the effects of another widely used pesticide, chlorpyrifos.

Bloomquist and his co-investigator, Dr. Bradley Klein, are supported by a five year, $584,558 grant from the United States Army Medical Research and Materiel Command. One purpose of the Neurotoxin Exposure Treatment Research Program, under which the project was funded, is to determine if military operational and deployment exposures increase risks for neurodegenerative disease and, if so, determine means of protecting troops.

“Permethrin is used worldwide in agriculture and urban settings,” Bloomquist said. “Widespread human exposure to this compound occurs, so its effects are not limited to soldiers.”

The talk, “Low-dose effects of insecticides to dopaminergic pathways involved in parkinsonism” (AGRO 31) will be presented at 2 p.m. Monday, March 24, in the Hampton Inn Convention Center Fulton room.

Mark Worsfold, 54, says he was handcuffed by Surrey police officers ‘for not smiling’ while watching men’s cycling road race

Olympics spectator with Parkinson’s wants ‘exoneration’ after arrest

Mark Worsfold, 54, says he was handcuffed by Surrey police officers ‘for not smiling’ while watching men’s cycling road race

‘for not smiling’ while watching men’s cycling road race

The London 2012 men’s cycling road race was watched by thousands of spectators who lined the route from central London to Box Hill in Surrey. Photograph: Miguel Medina/AFP/Getty Images

A man with Parkinson’s disease who was arrested during the Olympic men’s cycling road race while sitting beside the route has said he wants a “letter of exoneration” from Surrey police, claiming their treatment of him was disproportionate.

Mark Worsfold, 54, a former soldier and martial arts instructor, was arrested on 28 July for a breach of the peace shortly before the cyclists arrived in Redhouse Park, Leatherhead, where he had sat down on a wall to watch the race. Officers from Surrey police restrained and handcuffed him and took him to Reigate police station, saying his behaviour had “caused concern”.

“The man was positioned close to a small group of protesters and based on his manner, his state of dress and his proximity to the course, officers made an arrest to prevent a possible breach of the peace,” Surrey police said in a statement.

Worsfold, whose experience was first reported by Private Eye, claims police questioned him about his demeanour and why he had not been seen to be visibly enjoying the event. Worsfold, who was diagnosed with Parkinson’s in 2010, suffers from muscle rigidity that affects his face. He was released after two hours without charge or caution.

“It could have been done better. I was arrested for not smiling. I have Parkinson’s,” he said, adding that he realised the officers were working long hours and trying to control the event properly, but they had not, in his case, acted correctly. He said he did not want to make further comment until he received a response from Surrey police.

Worsfold, who teaches martial arts in Leatherhead, climbed Mount Kilimanjaro last February for the Save the Rhino charity.

Surrey police said: “There were a number of factors which led officers to make this arrest, including the fact that the race was rapidly approaching, the heightened level of security due to the high-profile nature of the event and the sheer number of spectators in attendance. These were fully explained to the individual concerned. He was given words of advice and released with no further action.”

They added that Worsfold had had “a number of knives” in his possession, but that these turned out to be made of rubber and for use only as display items.

The statement said: “Surrey police has received a letter from the man in which he has said that he ‘fully understands and appreciates the action taken by officers’. He has also said that he ‘appreciated and thanked both the arresting officers for their apologies and explanations’ following his release.”

Chief Superintendent Gavin Stephens said: “Officers were policing huge numbers of people during the Olympic events and in the interests of public safety they acted quickly and decisively based on the information available to them.”

Campaigners, however, said the incident was illustrative of the kind of “chronic misunderstandings” people with Parkinson’s have to deal with regularly. “Sadly Mark’s experience highlights the lack of understanding and compassion that many people currently living with Parkinson’s have to deal with every day,” said Laura Bowey, head of information and support at Parkinson’s UK.

“Despite affecting over 127,000 people in the UK, people with Parkinson’s are subject to chronic misunderstandings and misconceptions about the condition. All too frequently people with Parkinson’s tell us how are they are accused of being drunk, or acting suspiciously as they go about their daily lives.

“Parkinson’s is a complex condition, and those living with it can experience a range of different symptoms that can vary almost on an hourly basis. We hope that Mark’s experience will help to raise awareness of this distressing problem and will be a reminder to be careful about making the wrong assumptions about people who have Parkinson’s.”

Deer antlers inspire a new theory on osteoporosis

The loss of manganese could mean that calcium does not stick to bones and could cause osteoporosis. This is the new theory put forward by researchers at the University of Castilla-La Mancha (UCLM) in Spain after studying deer antlers. The hypothesis published this month in the Frontiers of Bioscience journal still needs to be confirmed by the scientific community.

Through the study of deer antlers, researchers of the Research Institute of Hunting Resources (IREC, joint centre UCLM-CSIC-JCCM) suggest that the origin of osteoporosis could not be directly linked to the lack of calcium but rather to the lack of a mineral essential to calcium absorption. In particular they believe that this could be manganese, according to a new theory published in the latest issue of the Frontiers of Bioscience journal.

According to Tomás Landete, sub-director of the IREC and one of team’s researchers, “previous antler studies show that manganese is necessary for calcium absorption. Our hypothesis is that when the human body absorbs less manganese or when it is sent from the skeleton to other organs that require it, such as the brain, the calcium that is extracted at the same time is then not properly absorbed and is excreted in the urine. It is in this way that osteoporosis can slowly strike.”

The theory must now be validated with more studies and medical trials but its creators believe that it is a “step in a totally new direction in osteoporosis research as it considers calcium loss to be a consequence of the disease and not the origin.”

The idea for the new proposal came from a dramatic increase in antler breakages seen in Spain in 2005. When scientists analysed these antlers in detail, they realised that weakening was due to manganese depletion caused by the deer’s diet. That year saw an intensely cold winter which in turn caused plants to reduce their manganese concentrations in response to such stress.

“Antlers grow by transferring 20% of the skeleton’s calcium towards their structure. We therefore saw that it was not calcium deficiency that caused the weakening but rather the deficiency of manganese,” clarifies Landete. “The lack of manganese was almost as if the ‘glue’ that sticks calcium to antlers bones was missing.”

Links to Alzheimer’s and Parkinson’s Disease

In the case of humans, the researchers suggest that manganese is extracted from the bones when it is required by the “most important” organs, such as the brain. The researcher adds that “maintaining the bones is important, but even more so is sustaining the working of the brain, which uses 25% of our energy intake when at rest.”

The team also points out that when this vital mineral runs out after the onset of osteoporosis, conditions like Alzheimer’s disease, Parkinson’s disease, and senile dementia could strike. To put this theory to the test, they analysed data from 113 patients who were operated on for osteoporosis and osteoarthritis (wear and tear of joint cartilage) at Hellín Hospital in Albacete, Spain between 2008 and 2009. Some 40% of those operated on for osteoporosis showed some form of cerebral dysfunction whereas this was not the case in any of the 68 patients operated on for osteoarthritis.

Furthermore, the percentage increased with age and only amongst those patients with osteoporosis. The exhaustion of manganese reserves could be behind the bone disease and the cerebral degeneration. “We are collecting human bones to confirm this. However, studies on rats in which Alzheimer’s disease has been induced by aluminium intoxication show that as the severity of this disease increases, manganese levels in the bones decrease,” says Landete.

The researcher also recalls studies that link manganese to Parkinson’s disease and show that astrocytes, which provide support to neurons, have specific enzymes that require manganese. In any case, researchers outline that their theory “is not a final solution to such diseases but constitutes the first step in a new direction” – a new direction that requires validation and confirmation from the scientific community.

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References:

Tomas Landete-Castillejos, Inmaculada Molina-Quilez, Jose Antonio Estevez, Francisco Ceacero, Andrés José García, Laureano Gallego. “Alternative hypothesis for the origin of osteoporosis: The role of Mn”. Frontiers in Bioscience (Elite Edition) 4: 1385-1390, January 2012. Doi: 10.2741/468