According to recently published research, scientists have created a method for creating in the lab a family of nerve cells linked in Parkinson’s disease using human stem cells.
These cells, which are located in the locus coeruleus (LC) area of the brain, generate norepinephrine, or NE, which is a signaling molecule. It is unknown precisely why these cells are known to deteriorate early in Parkinson’s disease and other neurological disorders.
The discovery of a protein crucial to the growth of the cells allowed the scientists to manufacture them in the laboratory. The team now hopes to use the stem cell model to more precisely examine neurodegenerative disease causes and to test new treatment possibilities.
Importantly, according to Yunlong Tao, PhD, the study’s first author, “we have some new understanding about locus coeruleus development.”
“That’s the major finding in this paper, and based on that finding, we are able to generate locus coeruleus norepinephrine neurons,” Tao said in a press release from the University of Wisconsin (UW)-Madison, where the study was conducted. Tao, an investigator at Nanjing University, in China, was working as a UW-Madison researcher at the time of the study.
The locus coeruleus, a small group of neurons located deep within the brain, is essential to brain activity. The primary norepinephrine producers in those cells are responsible for mediating the so-called fight-or-flight reactions that arise in stressful conditions. Norepinephrine is a signaling molecule.
Through a complex branching system, nerve cells originating in the locus coeruleus spread throughout the brain and spinal cord, releasing norepinephrine to control heart rate, blood pressure, arousal, memory, and attention.
“The norepinephrine neurons in the locus coeruleus are essential for our life,” said Su-Chun Zhang, MD, PhD, a neuroscience and neurology professor at UW-Madison and the study’s senior author.
“We call it the life center,” Zhang said, adding that “without these nerve cells, we would probably be extinct from Earth.”
Therefore, if this area of the brain malfunctions, it may have detrimental effects on overall brain health. Locus coeruleus-norepinephrine (LC-NE) cells have in fact been linked to a number of neurodegenerative illnesses, such as Alzheimer’s and Parkinson’s.
The locus coeruleus is one of the first areas of the brain to begin to degenerate in Parkinson’s disease. Numerous nonmotor symptoms of the disease have been linked to this.
“People have noticed this for a long time, but they don’t know what the function of the locus coeruleus is in this process,” Tao said, adding that’s also “partly because we don’t have a good model to mimic the human LC-NE neurons.”
Almost all adult cells in the body originate from stem cells, which under the correct circumstances can differentiate into almost any other type of cell. This can be used by scientists to create human-derived nerve cells in the laboratory. Researchers can get stem cells to differentiate into nearly any type of cell by treating them with particular substances.
With LC-NE neurons, this has previously proven challenging, and multiple attempts have failed.
In their latest investigation, the group discovered that controlling the proliferation of these cells requires a growth factor protein known as ACTIVIN-A. It is necessary for the gene activity that turns precursor cells into LC-NE neurons.
Thus, the scientists were able to create LC-NE neurons from stem cells by adding ACTIVIN-A during the process. The cells that were generated exhibited the anticipated anatomical and functional traits of LC-NE neurons, such as the release of NE and other activities associated with their function in respiration and heart rate.
In the end, the scientists think they may use the LC-NE cells to learn more about how and why these cells appear to go so quickly in conditions like Parkinson’s.
“If this is somewhat causative, then we could potentially do something to prevent or delay the neurodegeneration process,” Zhang said.
Neurons produced from stem cells will bear the cellular and genetic traits of the donor individual. To better understand how these cells function and react to potential treatments, researchers might therefore create LC-NE neurons from Parkinson’s patients.
“The availability of functional human LC-NE neurons enables investigation of their roles in psychiatric and neurodegenerative diseases and provides a tool for therapeutics development,” the researchers wrote.
In addition, the group created a line of cells equipped with a fluorescent sensor to measure norepinephrine levels. According to the researchers, this technology “may be useful to find novel drugs that regulate NE [norepinephrine] release and/or uptake.”
The researchers intend to investigate in greater detail how ACTIVIN-A controls the formation of LC-NE cells as a future step. Furthermore, the group intends to model human disease and evaluate medicines using the stem cell model.
“The application of these cells is quite broad in its significance,” Zhang noted.
