"Results and conclusions: Infection of late middle-aged mice with a particular strain of the bacteria Helicobacter pylori results in development of Parkinson�s disease symptoms (abnormal movement and brain chemistry) after 3-5 months. Feeding mice with extracts of killed H. pylori also induces these changes, indicating that a substance found in the bacteria is absorbed by the body and damages certain brain cells. Since H. pylori strains differ in their ability to cause inflammation and Parkinson�s disease, we suspect that bacterial factors and/or chronic inflammation also affect susceptibility to Parkinson�s disease. Our findings suggest that H. pylori infection could play a significant role in development of Parkinson�s disease in humans.
Significance and practical application: The cause of Parkinson�s disease has long been a mystery. Identifying H. pylori as one cause of Parkinson�s disease will encourage early treatment of H. pylori infection to prevent Parkinson�s disease development. Patients are currently screened for H. pylori infection only if they have ulcers or other stomach problems. Our mouse model will be used to reveal how H. pylori damages the brain. This could lead to improved treatment of, and possibly a cure for, many Parkinson�s disease patients.
Contributors: This work was carried out jointly by the laboratories of Traci L. Testerman, Ph.D. and Michael F. Salvatore, Ph.D. Drs. Testerman and Salvatore jointly designed the experiments. Dr. Testerman also infected the mice with Helicobacter pylori, prepared mouse chow containing killed H. pylori, and collected blood and gastric tissue for analysis. Dr. Salvatore analyzed brain tissue and oversaw locomotor testing. Locomotor testing was performed by Sandy Spann. Drs. Senkovich and McGee assisted with analysis of gastric tissue. All work was carried out at LSU Health Sciences Center-Shreveport in the Department of Microbiology and Immunology and the Department of Pharmacology, Toxicology, and Neuroscience. Work was funded by NIH grant R21AI085231-01A1 and LSUHSC-Shreveport intramural funding. The work is being presented at the American Society for Microbiology General Meeting on May 22, 2011 in New Orleans, LA.
Background, results, and implications: Physicians noted a correlation between stomach ulcers and Parkinson�s disease back in the 1960�s. At that time, Helicobacter pylori had not yet been discovered and ulcers were believed to result from stress. In the 1980�s, H. pylori was shown to cause more than 90% of gastric ulcers. Recently, a number of studies have found that people with Parkinson�s disease are more likely to be infected with H. pylori than people without Parkinson�s disease. Furthermore, H. pylori infection decreases the efficacy of a common medication used to treat Parkinson�s disease. In 1995, a clinical trial was performed to determine whether curing H. pylori infection in Parkinson�s disease patients could reduce disease progression. Patients who were cured of H. pylori showed slightly increased stride length and less rigidity in the months following treatment, whereas patients treated with placebo continued to deteriorate. These results suggest that treatment of H. pylori could at least slow Parkinson�s disease progression and possibly reduce symptoms. Unfortunately, this study also revealed a strong cautionary note. Antibiotic treatment does not always cure H. pylori infection. 20% of patients receiving antibiotics remained infected with H. pylori, and these patients deteriorated more rapidly than those who were not treated at all. Therefore, a physician wishing to treat a Parkinson�s disease patient for H. pylori infection faces a Russian roulette; there is an 80% chance that the patient will benefit from H. pylori treatment, but a 20% chance that the patient will become more debilitated.
Other scientists sought to explain why certain populations in Guam had a high risk of developing a disease called ALS-parkinsonism dementia complex. It was determined that a specific compound found in cycad seeds eaten by this population was neurotoxic. Evidently, this cycad toxin was traveling from the stomach to the brain. The cycad toxin has a structure similar to cholesterol with an attached sugar group. H. pylori has the curious ability to steal cholesterol from humans and attach a sugar group to it. As it turns out, the structure of the cycad toxin and the cholesterol modified by H. pylori are almost identical. This led to the hypothesis that uptake of the H. pylori-modified cholesterol could cause Parkinson�s disease.
An animal model was clearly needed in order to effectively study the role of H. pylori and its modified cholesterol in Parkinson�s disease. We infected young and aged (~55-65 in human years) mice with three strains of H. pylori. The SS1 ΔAlpAB strain showed the most significant reductions in locomotor activity and dopamine levels in the brain. The results were far more dramatic in aged mice than in young mice, demonstrating that normal aging increases susceptibility to parkinsonian changes in mice, as is seen in humans. The SS1 ΔAlpAB strain causes more severe gastric inflammation in animals than the parent strain, and blood tests show evidence for increased chronic inflammation throughout the body. This dovetails with evidence found by other researchers suggesting that inflammation contributes to Parkinson�s disease in humans.
In order to determine whether modified cholesterol or other substances could be responsible for Parkinson�s disease development, we fed aged mice with H. pylori extracts. These animals were not infected with H. pylori, but received H. pylori products orally. Mice fed with H. pylori extracts developed the same symptoms as those infected with H. pylori, demonstrating that modified cholesterol or other products contained within H. pylori contribute to disease development.
Our mouse model demonstrates a direct effect of H. pylori infection on development of Parkinson�s disease. Age dependence, locomotor defects, and neurodegeneration all parallel disease parameters seen in humans. The observation that not all H. pylori strains are equally able to cause Parkinson�s disease will allow us to investigate bacterial factors and/or immune response to H. pylori infection that increase the risk for Parkinson�s disease. Our ability to induce disease using H. pylori extracts will allow us to investigate how modified cholesterol or other substances are taken up in the GI tract and transmitted to the brain."
Posts: 845 | From Eastern USA | Registered: Jul 2006
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Lymeorsomething
Frequent Contributor (1K+ posts)
Member # 16359
posted
Yes, HP is probably more problematic than most people think. It has been suggested to play some role in endocrine disruption too, particularly with regard to GH levels and thyroid function.
Unfortunately, getting a decent gastro MD who can recognize the complexity of HP can be hard. The ones I've had didn't even recognize the abx I had been on. He asked me what Rifampin was? I mean c'mon!?
I had a physician's assistant ask me what triiodothyronine (T3) was... This is what we come up against not just for chronic lyme but for well-accepted issues like HP infection. It's mind boggling and self-education is so critical...
-------------------- "Whatever can go wrong will go wrong." Posts: 2062 | From CT | Registered: Jul 2008
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