Stem-cell-derived brain cells hold promise for Alzheimer’s, Parkinson’s research

Researchers on the University of Wisconsin–Madison have identified a protein key to the event of a sort of brain cell believed to play a task in disorders like Alzheimer’s and Parkinson’s diseases and used the invention to grow the neurons from stem cells for the primary time.

The stem-cell-derived norepinephrine neurons of the kind present in a component of the human brain called the locus coeruleus may enable research into many psychiatric and neurodegenerative diseases and supply a tool for developing latest ways to treat them.

Yunlong Tao, an investigator at Nanjing University in China who was a research professor at UW–Madison’s Waisman Center when the study was performed, and Su-Chun Zhang, a UW–Madison professor of neuroscience and neurology, published their work on the cells, which they call LC-NE neurons, today within the journal Nature Biotechnology.

Norepinephrine neurons within the locus coeruleus regulate heartbeat, blood pressure, arousal, memory, attention and “fight or flight” reactions. Humans have roughly 50,000 LC-NE neurons within the hindbrain, where the locus coeruleus is. From there, the LC-NE neurons reach into all parts of the brain and the spinal cord.

The norepinephrine neurons within the locus coeruleus are essential for our life. We call it the life center. Without these nerve cells, we’d probably be extinct from Earth.”

Su-Chun Zhang, professor of neuroscience and neurology, UW–Madison

These neurons also play a task, albeit unknown, in various neurodegenerative and neuropsychiatric diseases. In lots of neurodegenerative diseases resembling Alzheimer’s and Parkinson’s, the neurons start degenerating at a really early stage -; sometimes years before other brain regions begin to falter.

“People have noticed this for a very long time, but they do not know what the function of the locus coeruleus is on this process. And partly because we do not have model to mimic the human LC-NE neurons,” says Tao, first creator of the study.

Previous attempts at creating these neurons from human stem cells followed a protocol based on the event of LC-NE neurons in mouse models. For 2 years, Tao explored why these attempts were failing and the way development of the neurons from stem cells was different in humans.

In the brand new study, he identified ACTIVIN-A, a protein that belongs to a family of growth aspects, as vital in regulating neurogenesis in human NE neurons.

“We have now some latest understanding about locus coeruleus development,” Tao says. “That is the most important finding on this paper, and based on that finding, we’re capable of generate locus coeruleus norepinephrine neurons.”

To create LC-NE neurons, the researchers converted human pluripotent stem cells into cells from the hindbrain. Then, using ACTIVIN-A and a series of additional signals, they steered cell development toward their fate as LC-NE neurons.

Once converted, the cells showed typical characteristics of functioning LC-NE neurons within the human brain, releasing the neurotransmitter norepinephrine. Additionally they showed axonal arborization -; extension of the long, branching arms of neurons that enable the connections between brain cells -; and reacted to the presence of carbon dioxide, which is crucial for respiration control.

The brand new cells may function models for disease in humans, allowing scientists to screen drugs for potential treatments and answer questions resembling why the cells within the locus coeruleus die so early in neurodegenerative diseases.

“If that is somewhat causative, then we could potentially do something to stop or delay the neurodegeneration process,” Zhang says.

The LC-NE cells may someday function stem-cell therapy themselves.

“The applying of those cells is kind of broad in its significance,” Zhang says.

Next, the researchers plan to look at the detailed mechanisms through which ACTIVIN-A regulates LC-NE neuron development. The group can even use the cells for the translational work of drug screening and disease modeling.