Nav: Home

New study may reveal link to lipids playing a key role in Parkinson's disease

October 16, 2020

In a novel research study conducted by a team from the Neuroregeneration Institute at McLean Hospital, investigators believe they have found key brain cell type changes involving lipids, inflammation, and the development of Parkinson's disease (PD). Their findings appear in the current issue of the Proceedings of the National Academy of Sciences of the United States of America.

"Our study emphasizes the importance of cooperative use, storage, and transport of lipids between brain cell types in Parkinson's disease. Mechanisms involved in balancing cellular lipids--especially neutral lipids--such as we have characterized here, have been relatively understudied in the neurodegenerative diseases," explained Oeystein R. Brekk, PhD, an assistant neuroscientist at the Neuroregeneration Institute and first author of the study. "However, a wealth of knowledge already exists on such cellular lipid use, and consequences of lipid variations in other organs. For example, most people will know lipids from the role they play in increased risk for cardiovascular disease. Like the cardiovascular disease models, our Parkinson's disease and lipid-induced PD animal models point to lipid dependent pathological processes inside the brain, meaning we see dysregulation of the lipids and increased neuroinflammation."

In their study, Brekk and the McLean team demonstrate concurrent lipid changes in dopaminergic neurons and their neighboring brain glial cells, such as microglia and astrocytes in Parkinson's disease brains. Specifically, microglia and astrocytes showed abnormal patterns of intracellular lipid storage, which were significantly correlated with the accumulation of lipids within the dopaminergic neurons, the most vulnerable brain cells to the disease process. Overall lipid triglyceride content was statistically linked to a lipid-induced inflammatory stress marker in the brain tissue of PD patients. A remarkably similar brain cell and pathological picture was seen in an experimental animal model that simulates a Parkinson's disease genetically linked enzymatic loss-of-function in the glucocerebrosidase gene, leading to glycosphingolipid accumulation.

The work shows that microglia, which to a large extent are controlling macrophage and immune functions in the brain, are overloaded with lipids in Parkinson's disease, while astrocytes that normally supply lipids for maintenance and growth, on average, are losing some of that lipid content. At the same time, the neurons are accumulating lipids in an inverse linear fashion relative to the surrounding astrocytes. Moreover, the study shows that there is a statistically significant link between a molecule known as GPNMB. This stress immune response molecule is linked to astrocytes that typically appears to quench some of the inflammatory signals that are associated with lipid accumulation and overall triglyceride levels in the substantia nigra region of the brain.

"Remarkably, we can model these new findings in Parkinson's disease versus healthy aging, microglia and astrocyte interactions in the vulnerable brain regions, precisely by mechanisms that block a lysosomal lipid breakdown pathway, shown to be a strong risk factor for developing PD," said senior author Dr. Ole Isacson, founding director of the Neuroregeneration Institute at McLean Hospital and professor of neurology at Harvard Medical School. "These results support our lipid-inflammation hypothesis in the causation of Parkinson's disease initiation and progression and may help us discover and develop new therapies by leaving behind conventional thinking about PD pathology, which to some extent has been limited to neurons and protein aggregates."

According to Isacson, the next steps include exploring how these lipid cell-cell interactions in the brain are both adaptive and pathological over time and how such cell mechanisms can lead to Parkinson's disease and Lewy body dementia.
-end-
ABOUT McLEAN HOSPITAL:

McLean Hospital has a continuous commitment to put people first in patient care, innovation and discovery, and shared knowledge related to mental health. It is consistently named the #1 freestanding psychiatric hospital in the United States by U.S. News & World Report. McLean Hospital is the largest psychiatric affiliate of Harvard Medical School and a member of Mass General Brigham. To stay up to date on McLean, follow us on Facebook, YouTube, and LinkedIn.

McLean Hospital

Related Neurons Articles:

Paying attention to the neurons behind our alertness
The neurons of layer 6 - the deepest layer of the cortex - were examined by researchers from the Okinawa Institute of Science and Technology Graduate University to uncover how they react to sensory stimulation in different behavioral states.
Trying to listen to the signal from neurons
Toyohashi University of Technology has developed a coaxial cable-inspired needle-electrode.
A mechanical way to stimulate neurons
Magnetic nanodiscs can be activated by an external magnetic field, providing a research tool for studying neural responses.
Extraordinary regeneration of neurons in zebrafish
Biologists from the University of Bayreuth have discovered a uniquely rapid form of regeneration in injured neurons and their function in the central nervous system of zebrafish.
Dopamine neurons mull over your options
Researchers at the University of Tsukuba have found that dopamine neurons in the brain can represent the decision-making process when making economic choices.
Neurons thrive even when malnourished
When animal, insect or human embryos grow in a malnourished environment, their developing nervous systems get first pick of any available nutrients so that new neurons can be made.
The first 3D map of the heart's neurons
An interdisciplinary research team establishes a new technological pipeline to build a 3D map of the neurons in the heart, revealing foundational insight into their role in heart attacks and other cardiac conditions.
Mapping the neurons of the rat heart in 3D
A team of researchers has developed a virtual 3D heart, digitally showcasing the heart's unique network of neurons for the first time.
How to put neurons into cages
Football-shaped microscale cages have been created using special laser technologies.
A molecule that directs neurons
A research team coordinated by the University of Trento studied a mass of brain cells, the habenula, linked to disorders like autism, schizophrenia and depression.
More Neurons News and Neurons Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.