Caltech Team to Use $11M ASAP Grant to Study Gut-brain Connection

Yedida Y Bogachkov PhD avatar

by Yedida Y Bogachkov PhD |

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A team of researchers at Caltech will be looking into the interactions between the brain and the gut in Parkinson’s, in the hope of uncovering how their interaction may affect the disease.

Studies are noting abnormalities in the gastrointestinal environment of Parkinson’s patients, and a better understanding of “gut-brain connections” in this disease may lead to new ways of treating it.

The project is being funded by a grant of more than $11 million from the Aligning Science Across Parkinson’s (ASAP) initiative, according to a California Institute of Technology (Caltech) press release. Grant money came through The Michael J. Fox Foundation for Parkinson’s Research,  ASAP’s partner in implementing programs.

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Parkinson’s is characterized by the loss of neurons that produce the neurotransmitter dopamine — a chemical messenger that plays important roles in the brain and body — due to the accumulation of alpha-synuclein protein clumps.

Previous research showed evidence of gastrointestinal dysfunction in people with Parkinson’s, and animal model studies have linked alpha-synuclein in the gut to the alpha-synuclein clumps seen in patients’ brains.

Using animal models, Caltech researchers will further investigate if alpha-synuclein clusters in the gut can migrate to the brain, affecting neuronal circuits and ultimately leading to Parkinson’s symptoms.

“The team proposes that environmental and genetic factors impact the connections between neurons in the gastrointestinal nervous system, which can increase susceptibility to PD [Parkinson’s disease] triggers. These triggers include a-synuclein [alpha-synuclein], a protein that, when aggregated in clumps, is toxic to cells and can trigger both PD symptoms and gut inflammation,” Caltech stated in its release.

Researchers plan to map connections between the gut and the brain, and investigate whether disruptions in such connections might affect disease outcomes.

“Understanding the role that the gut–brain neural circuitry plays in PD will open new possibilities for treatments grantcould slow, halt, or even reverse symptoms,” the release stated.

Among the researchers involved in this project is Viviana Gradinaru, PhD, a professor of neuroscience and biological engineering and director of the Center for Molecular and Cellular Neuroscience at Caltech. Previous mouse work in Gradinaru’s lab indicated that protein aggregates could indeed spread from the gut to the brain via the vagus nerve, the longest nerve in the autonomic nervous system (part of the peripheral nervous system) that connects the stomach and small intestine to the brain (part of the central nervous system).

This spread, however, was only seen in older mice in this study — which also developed Parkinson’s-like symptoms — and not in young adult mice.

ASAP aims is to advance research and treatment discovery in Parkinson’s disease through collaboration, research-enabling resources, and data sharing.