Lab-Grown Nerve Tissue: A Key to Understanding Parkinson鈥檚 Disease
There is currently no cure for Parkinson鈥檚 disease, and researchers are still far from fully understanding the factors that trigger it. Helle Bogetofte Barnkob is determined to shed light on the disease by cultivating and studying nerve tissue in the lab.
Studying nerve cells is crucial for researchers investigating neurological diseases like Parkinson’s. This is also the case for Helle Bogetofte Barnkob, a medical doctor by training who has transitioned into research, now studying Parkinson’s disease at the Department of Biochemistry and Molecular Biology.
Since it is not possible to extract fresh nerve tissue from living human brains, Barnkob and her colleagues grow artificial nerve tissue in the lab.
These engineered tissues, known as brain organoids, are cultivated from stem cells and closely resemble human brain tissue, making them valuable for studying how environmental factors—such as pesticides—may contribute to Parkinson’s disease.
When ready for laboratory use, these brain organoids appear as tiny, whitish spheres about 2 mm in diameter. But how does Barnkob create them? And how does she conduct her experiments?
How to Grow Brain Organoids
A brain organoid starts as single stem cells, which grows alongside others on the bottom of a petri dish. The cells are treated with an enzyme that detaches them, allowing them to float freely. They are then transferred to specially designed petri dishes with small indentations that encourage them to cluster into round formations, each containing approximately 9,000 cells.
"We can produce hundreds of brain organoids simultaneously this way. The advantage of having so many is that we can conduct multiple types of analyses," Barnkob explains.
For her Parkinson鈥檚 research, Barnkob needs dopamine-producing nerve cells, like those found in the midbrain. These cells are particularly vulnerable to Parkinson鈥檚, and their gradual loss leads to the disease鈥檚 hallmark tremors and movement disorders.
To cultivate these crucial dopamine-producing cells, she adds growth factors that direct the stem cells to develop into exactly the right type鈥攅nsuring they become dopamine-producing neurons rather than other types of nerve cells.
After 40 days of growth, the brain organoids are sliced into ultra-thin, 300-micrometer sections and placed on thin membranes on top of a growth medium containing additional factors to support their development.
"This helps ensure the tissue gets enough oxygen. One challenge with organoids is that they lack blood vessels to transport oxygen to their core, causing central cells to die. This method prevents that. It also aids in nerve cell maturation, allowing them to develop the electrical activity necessary for communication," Barnkob explains.
Studying Pesticide Exposure
To measure the organoids' electrical activity, the research team uses a multi-electrode array, a specialized device equipped with a microchip containing 4000 tiny electrodes that can detect microvolt-level electrical signals.
Once the nerve cells in the organoids reach 80-100 days of age, they are mature enough for scientific experiments. Currently, Barnkob is investigating the potential effects of pesticide exposure.
"Certain pesticides are one of the environmental factors known to increase the risk of developing Parkinson’s. People at the highest risk are those who have been in direct contact with these pesticides, such as agricultural workers or individuals living near sprayed fields."
To simulate prolonged low-dose pesticide exposure, Barnkob adds tiny amounts of pesticide to the organoids' growth medium during each routine medium change.
"This mimics the type of exposure someone working with pesticides might experience. In these experiments, we’re particularly focused on whether alpha-synuclein accumulates in the nerve cells. Alpha-synuclein is a protein that builds up in the nerve cells of Parkinson’s patients."
Barnkob’s preliminary data suggest that this accumulation also occurs in her brain organoids when they are exposed to pesticides. However, many questions remain. Scientists still do not fully understand how pesticides influence alpha-synuclein accumulation or how they impact nerve cells more broadly.
"This is something I want to investigate further. We have strong expertise in proteomics at 糖果派对, and with our highly sensitive instruments, we can study both genetic and environmental risk factors over time. That is my next ambition."
Parkinson's Disease
Approximately 12,000 people in Denmark have Parkinson’s disease. A small percentage of cases are caused by specific genetic mutations, but the majority stem from other factors. Recent research has shown that people exposed to pesticides—such as farmers or those living near treated fields—face an increased risk of developing the disease. Parkinson’s symptoms, including severe tremors and movement disorders, occur when dopamine-producing nerve cells die. Dopamine is a neurotransmitter that regulates mood, emotions, and motor function. As these nerve cells degenerate, movement control becomes impaired. While medications can help alleviate symptoms, there is currently no cure for the disease.
Helle Bogetofte Barnkob
Helle Bogetofte Barnkob is a postdoc in Martin R酶ssel Larsen鈥檚 research group at the Department of Biochemistry and Molecular Biology, focusing on Parkinson鈥檚 disease. Previously, she studied rare genetic forms of the disease caused by specific gene mutations. Now, her focus is on the more common sporadic form, which arises from a combination of genetic and environmental risk factors. Helle originally trained as a medical doctor and holds a Ph.D. in neurobiology. She has conducted research at Harvard Medical School and the University of Oxford. Her work is supported by the Danish Parkinson鈥檚 Association, the Lundbeck Foundation, and the Beckett Foundation.