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UVA-China Research Breakthrough Promising for Brain Conditions

Brain cells talk to each other, and scientists have developed a way to listen in as neurons communicate in color-coded conversation – increasing hope for improved ways to treat brain and neurological conditions such as depression, schizophrenia and Alzheimer’s disease.

Credit goes to a new technique researchers have developed to visualize acetylcholine, a poorly understood neurotransmitter that “has an important role in how we behave because it affects our memory and mood,” said Dr. J. Julius Zhu of the University of Virginia School of Medicine and Department of Pharmacology. “It affects Alzheimer’s, schizophrenia, emotions, depression, all kind of emotion-related diseases and mental problems.”

Dr. J. Julius ZhuDr. J. Julius Zhu

Zhu worked with a team at his school in Charlottesville, Va., and colleagues in China to test the breakthrough, a method that involves using fluorescent color to observe neuron activity.

“Before, we didn’t have any way to understand how [such neurotransmissions] work,” said Zhu. “In the case of Alzheimer’s, in particular, we spent billions of dollars and we have almost no effective treatment. … Now, for the first time, we can see what is happening.”

Acetylcholine is also a factor in regulating blood pressure and stress, controlling insulin secretion in the pancreas and other critical bodily functions.

Drugs designed to combat Alzheimer’s disease inhibit acetylcholinesterase – an enzyme that “degrades” acetylcholine – in order to increase the effect of diminishing amounts of acetylcholine being released in the brain, Zhu said. But physicians don’t completely understood how the drugs work, and there has been no way to figure out exactly how much inhibition is needed.

“These drugs are not very effective,” said Zhu. “They only offer a minor improvement, and once you stop the drug [the symptoms] just seem much worse. So probably in trying to treat these patients, you temporarily enhance them but you actually make them even worse.”

But now, by seeing acetylcholine and other neurotransmitters in action in fluorescent color, doctors will be able to establish a baseline for good health and then work to restore that in patients.

“We want to first measure how [the neurotransmitters] normally do the job,” said Zhu. “We’ve already found that there are acetylcholine transmissions very different from what we would expect. Then we also want to find how the patient differs. That comparison will provide us important answers.”

The researchers have published their findings in the scientific journal Nature Biotechnology. Zhu co-directs the project with Dr. Yulong Li at Peking University in China. Miao Jing, Ph.D student at Peking University, and postdoctoral fellow Peng Zhang at UVA are the co-first authors. The other research team members are Guangfu Wang, Huoqing Jiang, Lukas Mesik, Jiesi Feng, Jianzhi Zeng, Shaohua Wang, Jess C. Looby, Nick A. Guagliardo, Linda W. Langma, Ju Lu, Yi Zuo, David A. Talmage, Lorna W. Role, Paula Q. Barrett, Li I. Zhang, Minmin Luo and Yan Song.

Supporting the work were 12 National Institutes of Health grants and the National Basic Research Program of China, the General Program of National Natural Science Foundation of China, the Junior Thousand Talents Program of China.

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