A growing body of evidence is forging a stronger and stronger connection between the onset of Parkinson’s disease and the gut. Scientists at Karolinska Institutet in Sweden and the University of North Carolina at Chapel Hill have thrown further weight behind this theory, with an investigation of cellular behavior in the nervous system of the digestive system revealing possible tell-tale signs at the earliest stages of the disease.

The notion that Parkinson’s disease could get its start in the gut has been around for some time, but in recent years we are seeing some compelling research that suggests our bellies may well play an important role in its onset. The disease is characterized by the cell death of neurons that secrete dopamine in the brain, which drives the motor impairments and other common symptoms of the illness.

What causes the demise of these neurons is not known for certain, but a leading hypothesis is that it is caused by aggregations of misfolded proteins known as Lewy bodies. An animal study last year produced the best evidence to date that these toxic protein clumps first form in the gut and move upward to the brain via the vagus nerve.

This new research hints at the role the enteric nervous system, as the regulator of digestive system, could play in these processes. Made up of a hundreds of millions of neurons, the body’s largest collection outside the brain, the enteric nervous system can operate independently of the central nervous system and for this reason is sometimes referred to as “the second brain.”

The authors of the new research studied gene expression in mice in combination with human genetics to systematically identify cell types that underly certain brain disorders. They then analyzed brain tissue taken from both healthy subjects and sufferers of Parkinson’s, taken at different stages of the disease. This revealed alterations in enteric neurons, “even at the earliest stages of disease progression,” the scientists write.

"As expected, we found that dopaminergic neurons were associated with Parkinson's disease,” says senior author Patrick Sullivan. “More surprisingly, we found that enteric neurons also seem to play an important role in the disorder, supporting the hypothesis that Parkinson's disease starts in the gut.”

The team’s research also produced another useful insight. By looking at these brain tissue samples taken at different points in disease progression, they found that important support cells in the brain called oligodendrocytes were impacted early on, even before the loss of the dopamine-producing neurons.

“These results suggest that oligodendrocyte could be an attractive target for therapeutic interventions as they appear to be affected before dopaminergic neurons,” says the Karolinska Institutet’s Julien Bryois, senior author of the study.

The research was published in the journal Nature Genetics.

Source: Karolinska Institutet via EurekAlert, University of North Carolina at Chapel Hill