Brain chemical lost in Parkinson’s may contribute to its own demise – Science News Magazine

Posted: September 7, 2017 at 5:47 pm

This post was added by Dr. Richardson

The brain chemical missing in Parkinsons disease may have a hand in its own death. Dopamine, the neurotransmitter that helps keep body movements fluid, can kick off a toxic chain reaction that ultimately kills the nerve cells that make it, a new study suggests.

By studying lab dishes of human nerve cells, or neurons, derived from Parkinsons patients, researchers found that a harmful form of dopamine can inflict damage on cells in multiple ways. The result, published online September 7 in Science, brings multiple pieces of the puzzle together, says neuroscientist Teresa Hastings of the University of Pittsburgh School of Medicine.

The finding also hints at a potential treatment for the estimated 10 million people worldwide with Parkinsons: Less cellular damage occurred when some of the neurons were treated early on with antioxidants, molecules that can scoop up harmful chemicals inside cells.

Study coauthor Dimitri Krainc, a neurologist and neuroscientist at Northwestern University Feinberg School of Medicine in Chicago, and colleagues took skin biopsies from healthy people and people with one of two types of Parkinsons disease, inherited or spontaneously arising. The researchers then coaxed these skin cells into becoming dopamine-producing neurons. These cells were similar to those found in the substantia nigra, the movement-related region of the brain that degenerates in Parkinsons.

After neurons carrying a mutation that causes the inherited form of Parkinsons had grown in a dish for 70 days, the researchers noticed some worrisome changes in the cells mitochondria. Levels of a harmful form of dopamine known as oxidized dopamine began rising in these energy-producing organelles, reaching high levels by day 150. Neurons derived from people with the more common, sporadic form of Parkinsons showed a similar increase but later, beginning at day 150. Cells derived from healthy people didnt accumulate oxidized dopamine.

This dangerous form of dopamine seemed to kick off other types of cellular trouble. Defects in the cells lysosomes, cellular cleanup machines, soon followed. So did the accumulation of a protein called alpha-synuclein, which is known to play a big role in Parkinsons disease.

Those findings are direct experimental evidence from human cells that the very chemical lost in Parkinsons disease contributes to its own demise, says analytical neurochemist Dominic Hare, of the University of Technology Sydney. Because these cells churn out dopamine, they are more susceptible to dopamines potential destructive forces, he says.

When researchers treated neurons carrying a mutation that causes inherited Parkinsons with several different types of antioxidants, the damage was lessened. To work in people, antioxidants would need to cross the blood-brain barrier, a difficult task, and reach the mitochondria in the brain. And this would need to happen early, probably even before symptoms appear, Krainc says.

Without this human model, we would not have been able to untangle the pathway, Krainc says. In dishes of mouse neurons with Parkinsons-related mutations, dopamine didnt kick off the same toxic cascade, a difference that might be due to human neurons containing more dopamine than mice neurons. Dopamine-producing neurons in mice and people have some very fundamental differences, Krainc says. And those differences might help explain why discoveries in mice havent translated to treatments for people with Parkinsons, he says.

Over the past few decades, scientists have been accumulating evidence that oxidized dopamine can contribute to Parkinsons disease, Hastings says. Given that knowledge, the new results are expected, she says, but still welcome confirmation of the idea.

These toxic cellular events occurred in lab dishes, not actual brains. Cell cultures arent the perfect re-creation of whats going on in the human brain, Hare cautions. But these types of experiments are the next best thing for monitoring the chemical changes in these neurons, he says.

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Brain chemical lost in Parkinson’s may contribute to its own demise – Science News Magazine

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