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High Intensity Interval Training May Benefit Patients with Parkinson’s, Pilot Study Shows

HIIT and Parkinson's

High intensity interval training for 12 weeks can significantly improve neuronal activity and delay progression of Parkinson’s disease, correlating with an improvement in patients’ quality of life, according to a recent study.

The scientific poster, “High intensity interval training elevates circulating BDNF and miRNAs level in patients with idiopathic Parkinson’s disease,” was presented recently at the International Congress of Parkinson’s Disease and Movement Disorders in Nice, France.

Different types of exercise — such as aerobic, resistance, forced exercise, dance and balance training — have been shown to improve motor symptoms in Parkinson’s disease.

However, to date, there is limited information about how exercise can induce beneficial effects, in particular regarding cognitive and motor functioning.

A team of Polish researchers conducted a small study to evaluate the impact of high-intensity interval training (HIIT) in people with Parkinson’s disease.

The study enrolled 32 idiopathic (of unknown cause) Parkinson’s patients, 16 of whom underwent 12 weeks of HIIT workout, and 16 age-matched participants used as controls. Patients were examined and had blood samples collected before and after the completion of HIIT workout (after 12 weeks) and one week after training completion.

Researchers evaluated the levels of brain-derived neurotrophic factor (BDNF), an important signaling molecule known to contribute for the normal activity of dopaminergic neurons — those most affected by Parkinson’s disease — and prevent their degeneration.

Recent studies have suggested that moderate intensity training can increase  the blood levels of BDNF in Parkinson’s patients while simultaneously decreasing physical impairment. Still, studies in sedentary subjects and athletes show better effectiveness of HIIT training as compared to aerobic training of moderate intensity.

The results showed that 12 weeks of HIIT resulted in higher BDNF levels and stimulated the production of small RNA molecules known to regulate BDNF.

Patients who underwent the HIIT workout plan also showed decreased Hoehn and Yahr scale scores, which indicate slower disease progression, neuroplasticity and, consequently, quality of life.

“This is a very interesting study that shows what is happening at a physiological level when patients with Parkinson’s disease exercise,” Deborah Hall, MD, PhD, director of the movement disorders program at Rush University Medical Center in Chicago, Illinois, said in a press release.

“Although neurologists are frequently asking their patients with [Parkinson’s] to exercise, not all patients are able or willing to do so, especially at levels used in many of the aerobic studies. By understanding what happens on a cellular or chemical level in these Parkinson’s disease exercisers who improve clinically, we may be able to provide an intervention or therapeutic that can lead to the same benefits as exercise without the work of exercising,” Hall said.

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PPMI RNA-Sequencing, the Largest Dataset of Gene Activity in Parkinson’s, Now Available to Researchers

PPMI RNA-Sequencing

The largest dataset ever compiled on Parkinson’s disease research — equivalent to 47.5 billion single-spaced typed pages — is now available to scientists, and can be used to investigate genetic changes over time in people with the neurodegenerative disorder.

Funded by the Michael J. Fox Foundation, the “Parkinson’s Progression Markers Initiative (PPMI) RNA-Sequencing Project” can help researchers assess how genetic changes observed in Parkinson’s impact disease progression or response to medication.

The study was led by Kendall Van Keuren-Jensen, PhD, at the Translational Genomics Research Institute (TGen), and David W. Craig, PhD, at the University of Southern California (USC).

A team of researchers analyzed samples obtained exclusively from the MJFF-sponsored Parkinson’s Progression Markers Initiative (PPMI), the most comprehensive study on PD until now. The PPMI study included more than 4,750 anonymous samples from 1,589 people with clinical and genetic PD risk factors and healthy control volunteers.

“PPMI has built the most robust Parkinson’s data set to date, collecting clinical, imaging and biological information from volunteers over at least five years to better understand disease onset and progression. The PPMI RNA-Sequencing Project significantly increases the study’s value and moves us closer to its goals to better define, measure and treat Parkinson’s disease,” Todd Sherer, PhD, the Foundation’s CEO, said in a press release.

Using a technique called RNA sequencing, researchers were able to analyze the entire RNA content of the PPMI samples. Analyzing the data — containing more than 108 terabytes of raw and processed sequencing data — took 480,000 hours of processing time, the researchers said.

All genetic information contained within genes, known as DNA, is ultimately translated into proteins. However, several complex steps exist before a protein can be produced. DNA is first transformed into RNA, after which a process called translation begins. That process gives rise to proteins.

By comparing the RNA levels of people with PD and controls, researchers can get a deeper understating of the key genes that play a role in the disease — and how their activity changes over time.

“Mutations in genes can affect proteins in ways that contribute to Parkinson’s disease, but that’s only part of the picture. To understand all the causes of the disease, we need reliable data on as many molecular measurements as we can: DNA, RNA and resulting proteins,” said Van Keuren-Jensen, co-director of the Center for Noninvasive Diagnostics at TGen, an affiliate of City of Hope.

“RNAs function as messengers from genes to create proteins, and many types of RNA have additional roles in cells that we are just beginning to understand. We sequenced these samples to capture as many types as possible, including protein-coding genes, lncRNAs and circular RNAs,” Keuren-Jensen added.

The RNA-sequencing data from the PPMI project is accessible to all researchers, who first need to apply for access through the PPMI website.

“Through PPMI, the Fox Foundation has created an unprecedented resource for the research community. And this RNA sequencing project is bringing another layer of information to explore and compare toward greater understanding of the disease and how to stop it,” said Craig, professor of translational genomics and co-director of the Institute of Translational Genomics at Keck School of Medicine of USC.

Data from the new study can be used to explore genetic changes associated with Parkinson’s and the impact of gene expression on factors including age, disease progression, and even medication use. Analysis of these data could help researchers better understand Parkinson’s, its variability, and ways to measure and treat it, the MJFF said.

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Genomic ‘Dark Matter’ Bridges Gap Between Parkinson’s, Other Neuropsychiatric Disorders, Study Finds

Researchers from the Brigham and Women’s Hospital and Harvard Medical School found more than 70,000 genetic sequences that do not encode proteins — called transcribed noncoding elements (TNEs) — active in dopamine neurons that are gradually lost over the course of Parkinsons’ disease.
Their findings indicate there may be a connection between these noncoding elements active in dopamine-producing neurons and genetic risk variants of Parkinson’s and other neuropsychiatric disorders, including addiction, schizophrenia, and bipolar disorder.
“We found that a whopping 64 percent of the human genome — the vast majority of which is ‘dark matter’ DNA that does not code proteins — is expressed in dopamine neurons in the human brain,” Clemens Scherzer, MD, a neurologist and genomicist who directs the APDA Center for Advanced Parkinson’s Disease Research and leads the Precision Neurology Program at Brigham and Women’s Hospital, said in a press release. “These are critical and specialized cells in the human brain, which are working sluggishly in Parkinson’s disease, but might be overactive in schizophrenia.”
The study, “Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease,” was published in Nature Neuroscience.
Using a new technique called laser-capture RNA sequencing, which allows researchers to analyze the entire RNA content of dopamine neurons cut out from human brain sections with a laser, Scherzer’s team analyzed more than 40,000 dopamine-producing neurons extracted from 86 post-mortem brains of subjects without a clinical diagnosis of neurodegenerative disease.
Data revealed that dopamine-producing neurons had a total of 71,022 TNEs, 33% of which were active enhancers — regulatory sites that work like “switches” to turn on the expression of specific genes in neurons. Many of these TNEs had never been described in the brain before, and most (57.5%) were exclusively expressed in human dopamine neurons, and not detected in other types of nerve cells.
Interestingly, a high percentage of the TNEs described were enriched in genetic variants of several neuropsychiatric disorders, including not only Parkinson’s, but also schizophrenia, bipolar disorder, and addiction.
“This work suggests that noncoding RNAs active in dopamine neurons are a surprising link between genetic risk, Parkinson’s and psychiatric disease,” Scherzer said. “Based on this connection we hypothesize that the risk variants might fiddle with the gene switches of dopamine-producing brain cells.”
Scherzer’s team has compiled all the findings in a publicly available database called BRAINcode they hope will contribute to advancing studies focused on defining disease targets and biomarkers for Parkinson’s and other neuropsychiatric disorders.
“It has clear applications for the genetics of more than 20 million patients in the United States alone with perturbed dopamine systems, in narrowing the search window for functional associations and therapeutic nodes, and for defining the regulatory networks that underpin this archetype of a human brain neuron,” the researchers wrote in the study.
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Source: Parkinson's News Today