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Parkinson’s May Originate From Alpha-Synuclein Migrating From the Gut, Rat Study Shows

gut Parkinson's alpha-synuclein

New experimental evidence collected from rats shows that alpha-synuclein — the protein that causes Parkinson’s disease — can travel from the intestines to other organs, such as the heart and brain.

These findings, reported in the study “Evidence for bidirectional and trans-synaptic parasympathetic and sympathetic propagation of alpha-synuclein in rats,” provide further support to the hypothesis that the development of Parkinson’s disease is directly linked to the intestinal system.

The study was published in Acta Neuropathologica.

A hallmark feature of Parkinson’s is the progressive degeneration of brain cells due to the accumulation of toxic clumps of alpha-synuclein, called Lewy bodies.

Prior work in postmortem human brains has shown that the misfolded protein primarily accumulates in brain areas controlling movement, which explains the characteristic motor symptoms associated with the disease. But that work also revealed the protein’s accumulation in the vagus nerve – which connects the brain to the gut.

This led to the theory that Parkinson’s progression could require communication between the gut and the brain.

To further explore this association, researchers from Aarhus University and its clinical center, in Denmark, conducted a new study in rats. The team used rats that were genetically modified to produce excessive amounts of alpha-synuclein, and which were susceptible to accumulating harmful versions of the protein in nerve cells. Human alpha-synuclein or an inactive placebo was injected into the small intestines of these rats.

With this approach, the investigators found that both groups of rats — those injected with alpha-synuclein or placebo — had high levels of the protein in the brain. However, only those injected with alpha synuclein showed Parkinson’s characteristic clump build-up patterns, which affected the motor nucleus and substantia nigra in the brain.

“After two months, we saw that the alpha-synuclein had travelled to the brain via the peripheral nerves with involvement of precisely those structures known to be affected in connection with Parkinson’s disease in humans,” Per Borghammer, an Aarhus University professor and the study’s senior author, said in a press release written by Mette Louise Ohana.

“After four months, the magnitude of the pathology was even greater. It was actually pretty striking to see how quickly it happened,” Borghammer said.

Alpha-synuclein also was found to accumulate in the heart and stomach, which suggests a secondary propagation pathway. That pathway likely is mediated by the celiac ganglia, which are abdominal nerve bundles that innervate the gastrointestinal tract.

A recent study conducted by researchers at Johns Hopkins University School of Medicine revealed similar data, but in mice. The Hopkins team also found that, when they injected an altered form of alpha-synuclein in the intestine of mice, it would first accumulate in the vagus nerve and subsequently spread throughout the brain.

With the findings from the new study, researchers now have more detailed evidence on how the disease most likely spreads.

This may put the scientific community one step closer toward developing more effective medical strategies to halt the disease, Borghammer said.

“For many years, we have known that Parkinson patients have extensive damage to the nervous system of the heart, and that the damage occurs early on. We’ve just never been able to understand why. The present study shows that the heart is damaged very fast, even though the pathology started in the intestine, and we can continue to build on this knowledge in our coming research,” he said.

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Magnetic Gene in Fish May Help Develop New Treatment Strategies for Parkinson’s, Study Says

magnetic gene in fish

A fish that can sense the Earth’s magnetic field while it swims could help scientists understand how the human brain works and eventually unlock strategies to help control movement impairments in patients with Parkinson’s disease and other neurological disorders, a study reports.

The study, “Wireless control of cellular function by activation of a novel protein responsive to electromagnetic fields,” was published in the journal Scientific Reports.

The freshwater glass catfish, also known as Kryptopterus bicirrhis, is capable of sensing and responding to the Earth’s electromagnetic fields.

Michigan State University (MSU) researchers were able to identify this “navigational gene,” called the electromagnetic-perceptive gene, or EPG. The protein produced by the EPG senses both static and alternating magnetic waves, allowing the fish to swim away in response to magnetic fields.

The team injected a virus containing the EPG into motor neurons located in one of the main regions of the brain involved in motor function, called the right primary motor cortex, of 10 adult rats. Five control rats were injected with a virus that had a fluorescent protein called GFP instead of the EPG.

Remote wireless magnetic stimulation of EPG-expressing rats induced large muscle responses compared with control rats.

“We’ve found a noninvasive way to activate this gene once injected in the brain cells of mice and regulate movement in their limbs,” Galit Pelled, PhD, a medical bioengineering professor at MSU’s Institute for Quantitative Health Science and Engineering and the study’s lead author, said in a press release.

These findings suggest that the same strategy “could work similarly in humans,” he said.

In the future, a Parkinson’s disease patient with tremors could receive an injection of the EPG gene in a specified brain region. A magnet that emits electromagnetic waves could then activate the gene to help control, or ideally stop, the tremors.

“Technology is getting better and better every year, so this magnet could be built into anything,” Pelled said.

Deep brain stimulation, an established treatment for advanced Parkinson’s patients, is a surgical procedure that involves implanting a neurostimulator in the brain, which sends electrical impulses to specific brain regions.

However, this technique is highly invasive involving drilling a hole in the skull for electrode implantation. This process can damage neurons and other cells and even increase the levels of inflammatory factors.

Engineering stem cells to express the EPG gene and introducing them into the brain of Parkinson’s patients is the goal of Assaf Gilad, PhD, the study’s co-author and a professor of biomedical engineering and radiology.

“Stem cells are very good carriers of genes so if someone has Parkinson’s, we can introduce these stem cells into the brain as a therapy,” he said. “This type of treatment could not only help the brain, but could work in other parts of the body too, like the heart, and help those with heart issues.”

Researchers are now trying to understand the underlying mechanisms that allow the EPG gene to respond to magnetic waves.

“The mechanism of the gene is still unknown,” Gilad said. “But once we understand how it really works, it could open the door to even more possibilities.”

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Source: Parkinson's News Today

Levodopa May Not Be the Best Option for Parkinson’s Treatment, Study by Students Contends

Levodopa shortcomings

Levodopa improves Parkinson’s patients’ symptoms by binding with two types of receptors for dopamine, a neurotransmitter that helps regulate movement and emotional response.

Although it is considered the gold standard in Parkinson’s treatment, a study from Binghamton University students contends that levodopa’s interaction with the dopamine receptor D2 may cause involuntary muscle movements, compulsive behaviors, and hallucinations.

The research, “Effects of Receptor-Specific Dopamine Drugs on the Treatment of Cognitive Deficits in Parkinson’s Disease,” appeared in the The Undergraduate Journal of Psychology at UCLA.

Parkinson’s is a progressive neurodegenerative disorder that affects movement, muscle function, and speech. It is characterized by gradual loss of nerve cells that contain the neurotransmitter dopamine. They are located in a brain area called substantia nigra that is essential to the control of movement.

Dopamine binds to two classes of receptors — D1 and D2. Levodopa, which is also called L-DOPA, is a naturally occurring molecule that generates dopamine. It binds to both D1 and D2 receptors to replenish the disease-related lower levels of dopamine, improving Parkinson’s symptoms.

The New York State university research team triggered the formation of brain lesions in rats to mimic the loss of nerve cells in Parkinson’s. Rats were then treated with levodopa or compounds that bind with either D1 or D2 receptors, but not both. The next step was for rats to be tested for movement, ability to pay attention, and spatial memory.

Although activating D2 receptors with quinpirole improved the rats’ spatial memory, it led to  attention loss in both rats with brain lesions and controls. In contrast, activating D1 receptors did not lead to significant differences, in comparison with levodopa.

Overall, the findings suggested that, because levodopa stimulates D2 receptors, it may not be the best choice for Parkinson’s treatment.

“Parkinson’s disease is one of the most common neurodegenerative diseases in the world,” Lakshmi Hareendran, a member of the research team, said in a press release. “Knowing that the current treatment isn’t as effective as it could be is important.”

“In conclusion, the quinpirole effects on memory and attention ability is an essential discovery. Uncovering the mechanisms underlying these actions may lead to the development of a more effective treatment for [Parkinson’s] that covers both motor and cognitive deficits in humans,” the researchers wrote.

Hareendran comes from a family with several doctors and has an uncle who is a brain surgeon. “As a kid, just thinking about him being able to understand something as complex as the human brain really inspired me to go down that path,” she said. She plans to work with Doctors Without Borders some day.

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Source: Parkinson's News Today