Long-distance skiers may have 'motor reserve' that can delay onset of Parkinson's disease
February 11, 2020
Science Daily IOS Press
To better understand the relationship between physical activity and Parkinson's Disease (PD) investigators in Sweden analyzed medical records of nearly 200,000 long-distance skiers who took part in the Vasaloppet cross-country ski race. They established that a physically active lifestyle is associated with close to a 30% reduced risk for PD, which might be explained by a motor reserve among the physically active, however, this dissipates as individuals age. Their results are published in the Journal of Parkinson's Disease (JPD).
Studies have shown the enormous benefits of exercise in many disorders including neurodegenerative diseases, but the reasons are not always clear. "Exercise seems to protect against the motor symptoms of PD but not necessarily against the brain damage caused by PD," explained co-lead investigator Tomas T. Olsson, MD, Department of Neurology, Skåne University Hospital, and Department of Experimental Medical Science, Experimental Dementia Research Unit, Lund University, Lund, Sweden.
"To understand the mechanisms behind the protective effects of exercise it is very important to establish whether exercise gives people a greater reserve or direct protection," noted co-lead investigator Martina Svensson, Department of Experimental Medical Science, Experimental Neuroinflammation Laboratory, Lund University, Lund, Sweden.
To investigate the degree to which physical activity is associated with long-term lower risk of PD and whether this association can be explained by physically active people being able to sustain more PD neuropathology before the onset of clinical symptoms, investigators analyzed long-term data about the incidence of PD among long-distance skiers. They followed 197,685 participants (median age 36 years; 38% women) in the Vasaloppet, an annual cross-country ski race of up to 90 km, from 1989 to 2010 and compared them to 197,684 age-matched non-skiers. Incidence of PD was taken from the Swedish National Patient Registry
Investigators found that the skiers were almost 30% less likely to develop PD than non-skiers. However, this dissipates with time and increasing age and results in diagnoses of PD among skiers matching the general population.
"We speculate that this would be consistent with the hypothesis that individuals who are physically well-trained have a greater motor reserve, which for every given level of Parkinson's brain damage would result in less motor symptoms thus delaying the diagnosis of PD," noted senior investigator Tomas Deierborg, PhD, Department of Experimental Medical Science, Experimental Neuroinflammation Laboratory, Lund University, Lund, Sweden. "This is analogous to the well-established concept of cognitive reserve in dementia in which the well-educated can sustain more brain pathology without clinical dementia. It highlights the importance of staying physically active throughout life in order to have a reserve to better cope when the frailties and diseases of old age inevitably arrive."
"If a person is physically active, it may be possible to maintain mobility for longer, despite the pathological changes in the brain," added Dr. Olsson.
JPD's Co-Editor-in-Chief Bastiaan R. Bloem, MD, PhD, Director, Radboudumc Center of Expertise for Parkinson & Movement Disorders, Nijmegen, The Netherlands, commented, "There is an enormous interest in developing new therapies that can help to lower the risk of developing PD. This present study by Olsson and colleagues is particularly exciting in that regard, because it suggests that a readily available intervention -- exercise -- can actually achieve this. The study also provides an explanation why exercise does not offer a complete protection against PD; it supports the motor reserve of the brain, and as such, probably helps to postpone rather than fully prevent the onset of manifest Parkinson symptoms."
PD is a slowly progressive disorder that affects movement, muscle control and balance. It is the second most common age-related neurodegenerative disorder affecting about 3% of the population by the age of 65 and up to 5% of individuals over 85 years of age.
https://www.sciencedaily.com/releases/2020/02/200211104915.htm
Can pomegranate juice protect the infant brain?
August 21, 2019
Science Daily/Brigham and Women's Hospital
In ongoing investigations, clinical researchers are exploring whether pomegranate juice intake during pregnancy can have a protective effect.
When it comes to protecting the newborn brain, taking steps to mitigate risk before birth may be critical. Some newborns, such as those with intrauterine growth restriction (IUGR), are at heightened risk. Being able to intervene before birth to aid in protecting the newborn brain may prevent the often-devastating effects of brain injury. In ongoing investigations, clinical researchers from Brigham and Women's Hospital are exploring whether pomegranate juice intake during pregnancy can have a protective effect. In a paper appearing in PLOS One, the team presents its preliminary findings from a clinical trial of expectant mothers whose babies were diagnosed with IUGR. The exploratory study, supported by National Institute of Health Grants, The Foundation for Barnes-Jewish Hospital and an unrestricted gift from POM Wonderful, shows promise, with evidence of better brain development and brain connectivity in infants born to mothers who consumed pomegranate juice daily. A second, larger clinical trial is currently underway at the Brigham to validate these findings.
"Our study provides preliminary evidence suggesting potential protective effects for newborns exposed to pomegranate juice while in utero," said senior author Terrie Inder, MBCHB, chair of the Department of Pediatric Newborn Medicine at the Brigham. "These findings warrant continued investigation into the potential neuroprotective effects of polyphenols in at-risk newborns, such as those with hypoxic-ischemic injury."
In cases of IUGR, a baby in the womb is measuring small for its gestational age, often because of issues with the placenta, which brings oxygen and nutrients to the growing fetus. One out of every 10 babies is considered to have IUGR. The process of birth itself can further decrease blood flow or oxygen to the baby, including to the baby's brain. If this is very severe, it can result in a condition known as hypoxic-ischemic injury, which contributes to almost one-quarter of newborn deaths worldwide.
Polyphenols, which include tannic acid and ellagitannins, are part of a class of antioxidants found in many foods and beverages, including nuts, berries, red wine and teas. Pomegranate juice is a particularly rich source of these molecules. Polyphenols are known to cross the blood-brain barrier, and studies in animal models have demonstrated protective effects against neurodegenerative diseases. To date, no clinical studies had evaluated the potential effects of giving pregnant women pomegranate juice to protect the brains of at-risk newborns.
The current randomized, controlled, double-blinded study enrolled 78 mothers from Barnes-Jewish Hospital obstetric clinic in St. Louis with IUGR diagnosed at 24-43 weeks' gestation. Women were randomized to receive 8 ounces of pomegranate juice daily or a taste/calorie matched placebo that was polyphenol free. Women drank the juice daily from enrollment until delivery. The team measured several aspects of brain development and injury, including infant brain macrostructure, microstructural organization and functional connectivity.
While the team did not observe differences in brain macrostructure, they did find regional differences in white matter microstructure and functional connectivity.
"These measures tell us about how the brain is developing functionally," said Inder. "We saw no difference in brain growth and baby growth, but we did see improvement in cabling network and brain development measured by synchronous blood flow and visual development of the brain."
The authors note that the findings warrant the need for a larger, rigorously designed clinical trial to allow continued investigation into the potential neuroprotective effects of polyphenols. Such a study is now underway at the Brigham.
"We plan to continue investigating these exciting findings," said Inder. "While the preliminary evidence shows promise, additional study and replication is needed."
https://www.sciencedaily.com/releases/2019/08/190821142719.htm
Circadian clock plays unexpected role in neurodegenerative diseases
Seemingly counterintuitive evidence shows that disrupted sleep protects the brain
April 2, 2019
Science Daily/Northwestern University
Researchers induced jet lag in a fruit fly model of Huntington disease and found that jet lag protected the flies' neurons.
While your body might bemoan the many uncomfortable effects of jet lag, your brain may be thanking you for that cross-time zone travel.
In a new study, Northwestern University researchers induced jet lag in a fruit fly model of Huntington disease and found that jet lag protected the flies' neurons. The team then identified and tested a circadian clock-controlled gene that, when knocked down, also protected the brain from the disease.
The findings reveal potential new treatment pathways to slow the progression of or prevent neurodegenerative diseases.
"It seems counterintuitive, but we showed that a little bit of stress is good," said Northwestern's Dr. Ravi Allada, a circadian rhythms expert who led the research. "We subtly manipulated the circadian clock, and that stress appears to be neuroprotective."
The study will be published April 2 in the journal Cell Reports. Allada is the Edward C. Stuntz Distinguished Professor and chair of the department of neurobiology in Northwestern's Weinberg College of Arts and Sciences.
Patients with neurodegenerative diseases often experience profound disruptions in their circadian rhythms, or sleep-wake cycles. They may sleep more than usual or lose the ability to stay asleep. This can lead to nighttime wandering, increased agitation, general stress and a decreased quality of life.
"We have long known that a disrupted clock is an early indicator of neurodegenerative disease," Allada said. "In many cases, sleep disruption precedes any other symptom. But we didn't know whether the circadian disruption is a cause of the disease or a consequence of the disease."
To probe this question, Allada employed the fruit fly model of Huntington disease, a well-studied model organism for both circadian rhythms and neurodegenerative diseases. Although fruit flies might seem completely different from humans, the neurons that govern flies' sleep-wake cycles are strikingly similar to humans'. Fruit flies that have the mutant Huntington gene also demonstrate similar symptoms as humans with the disease: reduced lifespan, motor deficits, neurodegeneration, disrupted circadian rhythms and an accumulation of diseased proteins in the brain, which aggregate and cause neurons to die.
"Normally, fruit flies wake up, get very active, then go to sleep and become inactive," Allada explained. "It's a 24-hour pattern. In the Huntington model, there is no rhythm. The flies wake up and fall asleep all the time."
Allada's team altered the flies' circadian rhythms two different ways. For one group of flies, the researchers altered the flies' environment by changing the daily timing of light-dark cycles. This manipulation caused the flies to live a 20-hour day instead of a 24-hour day. And for another group of flies, the researchers mutated a gene that is well known for controlling the internal circadian clock.
"We essentially gave the flies jet lag for every day of their lives," Allada said. "It's like traveling four hours east every day."
In both cases, the mutant Huntington disease proteins aggregated less and fewer neurons died. Allada, who expected jet lag to inflict even more damage on the brain, was surprised. "We had wondered if the clock played a role in the disease," he said. "It turned out that the clock was important -- but in a manner that we did not predict."
Allada and his team were so fascinated by the result that they took the study one step further. They decided to screen through dozens of clock-controlled genes to pinpoint one that also might similarly protect the brain against neurodegenerative diseases.
The team zeroed in on a gene that encodes the "heat shock organizing protein," or "hop" for short. Not only is hop controlled by the body's circadian clock, the gene is also responsible for protein folding. Because misfolded proteins can result in many different neurodegenerative diseases, Allada thought hop made an interesting target. He and his team knocked down the hop gene in flies with the protein that causes Huntington disease and -- again -- were surprised. Knocking down the gene restored the flies' arrhythmic circadian clocks, reduced the aggregation of diseased proteins in the brain and reduced the number of neurons killed by those proteins.
"We thought that inhibiting this gene that helps your proteins fold properly would make things worse, but they got better," Allada said. "It again shows that a little bit of stress is probably good."
Next, Allada plans to test this method in a fruit fly model of Alzheimer's disease. He believes that targeting and knocking down the hop gene could potentially be an early intervention for slowing the progression of various neurodegenerative diseases.
https://www.sciencedaily.com/releases/2019/04/190402113220.htm
Native California medicinal plant may hold promise for treating Alzheimer's
Salk scientists identify possible healing compound in Yerba santa
February 20, 2019
Science Daily/Salk Institute
The medicinal powers of aspirin, digitalis, and the anti-malarial artemisinin all come from plants. A discovery of a potent neuroprotective and anti-inflammatory chemical in a native California shrub may lead to a treatment for Alzheimer's disease based on a compound found in nature.
"Alzheimer's disease is a leading cause of death in the United States," says Senior Staff Scientist Pamela Maher, a member of Salk's Cellular Neurobiology Laboratory, run by Professor David Schubert. "And because age is a major risk factor, researchers are looking at ways to counter aging's effects on the brain. Our identification of sterubin as a potent neuroprotective component of a native California plant called Yerba santa (Eriodictyon californicum) is a promising step in that direction."
Native California tribes, which dubbed the plant "holy herb" in Spanish, have long used Yerba santa for its medicinal properties. Devotees brew its leaves to treat respiratory ailments, fever and headaches; and mash it into a poultice for wounds, sore muscles and rheumatism.
To identify natural compounds that might reverse neurological disease symptoms, Maher applied a screening technique used in drug discovery to a commercial library of 400 plant extracts with known pharmacological properties. The lab had previously used this approach to identify other chemicals (called flavonoids) from plants that have anti-inflammatory and neuroprotective properties.
Through the screen, the lab identified a molecule called sterubin as Yerba santa's most active component. The researchers tested sterubin and other plant extracts for their impact on energy depletion in mouse nerve cells, as well as other age-associated neurotoxicity and survival pathways directly related to the reduced energy metabolism, accumulation of misfolded, aggregated proteins and inflammation seen in Alzheimer's. Sterubin had a potent anti-inflammatory impact on brain cells known as microglia. It was also an effective iron remover -- potentially beneficial because iron can contribute to nerve cell damage in aging and neurodegenerative diseases. Overall, the compound was effective against multiple inducers of cell death in the nerve cells, according to Maher.
"This is a compound that was known but ignored," Maher says. "Not only did sterubin turn out to be much more active than the other flavonoids in Yerba santa in our assays, it appears as good as, if not better than, other flavonoids we have studied."
Next, the lab plans to test sterubin in an animal model of Alzheimer's, then determine its drug-like characteristics and toxicity levels in animals. With that data, Maher says, it might be possible to test the compound in humans, although it would be critical to use sterubin derived from plants grown under standardized, controlled conditions. She says the team will likely generate synthetic derivatives of sterubin.
https://www.sciencedaily.com/releases/2019/02/190220174105.htm