Nerve Damage in Hearts of Parkinson’s Patients Can Be Monitored with Imaging Tools, Animal Study Reports

Cardiovascular damage in Parkinson’s patients, due to nerve cell loss in the heart, can be captured by imaging stress and inflammation molecules — a process that may help to determine the mechanisms behind such damage and ways of treating neurodegeneration in the heart, researchers report.

The study by researchers at the University of Wisconsin-Madison, “In vivo imaging of inflammation and oxidative stress in a nonhuman primate model of cardiac sympathetic neurodegeneration,” was published in the journal npj Parkinson’s Disease.

Virtually all Parkinson’s patients experience, to some extent, a loss of the nerve cells controlling the heart, specifically those involved in the sympathetic nervous system that regulates the heartbeat in response to changes in physical activity and blood pressure. This degeneration is independent of motor symptoms and can lead to fatigue, exercise difficulties (poor cardiac response), and dizziness and fainting, putting patients at a greater risk of falls and injury.

“This neural degeneration in the heart means patients’ bodies are less prepared to respond to stress and to simple changes like standing up,” Marina Emborg, the study’s senior author, a UW-Madison professor, and a researcher at the Wisconsin National Primate Research Center, said in a university news article by Chris Barncard.

Because nearly 60 percent of Parkinson’s patients have evidence of cardiac nerve loss at diagnosis, it has been suggested that tests of such damage might be a Parkinson’s marker  in patients considered at disease risk but asymptomatic in terms of tremors or motor control.

The researchers created radio-labeled compounds that could monitor nerve loss through positron emission tomography (PET) scans.

The compounds target molecules involved in inflammation and oxidative stress, which are believed to play a key role in Parkinson’s neurodegeneration.

Investigators tested three radioligands – PBR28, ATSM, and MHED – in monkeys with induced cardiac nerve cell loss, mimicking the features of Parkinson’s in humans. These compounds had been deemed safe in mice and humans.

The monkeys underwent PET scans, a imaging approach that detects radio-labeled compounds, once before and twice after receiving the molecules.

Researchers focused particularly on changes in the left ventricle, the strongest blood-pumping chamber of the heart, and found that they could trace damage, inflammation, and oxidative stress over time.

“We know there is damage in the heart in Parkinson’s, but we haven’t been able to look at exactly what’s causing it,” said Jeanette Metzger, the study’s first author. “Now we can visualize in detail where inflammation and oxidative stress are happening in the heart, and how that relates to how Parkinson’s patients lose those neuronal connections in the heart.”

Researchers also hypothesized that the tracers could be used to monitor the efficacy of treatments aiming to protect these neurons. They tested a drug called pioglitazone – approved to treat diabetes by lowering blood sugar levels – because it has anti-inflammatory and anti-oxidative effects.

Compared to placebo monkeys, those given pioglitazone were found to be significantly better at preventing signs inflammation and oxidative stress in the heart, which ultimately was associated with reduced nerve cell damage.

“The recovery of nerve function is much greater in the pioglitazone-treated animals,” Emborg said. “And what’s interesting is this method allows us to identify very specifically the differences the treatment made — separately for inflammation and for oxidative stress — across the heart.”

The researchers suggested this new technique may  be useful in better understanding the mechanisms of early nerve damage occurring in the hearts of Parkinson’s patients, as well as those with other cardiac disorders.

“The present study in rhesus macaques demonstrated that PET with the radioligands MHED, PBR28, and ATSM successfully detected changes over time and across the cardiac left ventricle in sympathetic innervation, inflammatory response, and oxidative stress during neurotoxin-induced neurodegeneration and PPARγ [pioglitazone]-associated neuroprotection,” they wrote.

“Our findings strongly support future preclinical and clinical studies using these radioligands to evaluate the role of inflammation and oxidative stress in peripheral sympathetic neurodegeneration,” the study concluded.