Drug Combination Generates New Neurons from Neighboring Cells

In a study published in Stem Cell Reports, scientists at Penn State University have developed a drug cocktail that converts neighboring cells—often known as glial cells-- of damaged neurons into functional new neurons. The study could open doors to treating stroke, Alzheimer's disease, and brain injuries. Glial cells normally provide support and insulation for neurons.

" The biggest problem for brain repair is that neurons don't regenerate after brain damage, because they don't divide," explain researchers. "In contrast, glial cells, which gather around damaged brain tissue, can proliferate after brain injury. I believe turning glial cells that are the neighbors of dead neurons into new neurons is the best way to restore lost neuronal functions."

The current research study tested various numbers and combinations of molecules that will identify a streamlined approach to the reprogramming of astrocytes, a type of glial cells, into neurons. The result was chemically converted neurons that can survive for a while in a culture dish. These neurons form robust neural networks that send electrical and chemical signals for communication—just as normal neurons do.

"We identified the most efficient chemical formula among the hundreds of drug combinations that we tested," says a researcher. "By using four molecules that modulate four critical signaling pathways in human astrocytes, we can efficiently turn human astrocytes -- as many as 70 percent -- into functional neurons."

"The most significant advantage of the new approach is that a pill containing small molecules could be distributed widely in the world, even reaching rural areas without advanced hospital systems," he said. "My ultimate dream is to develop a simple drug delivery system, like a pill, that can help stroke and Alzheimer's patients around the world to regenerate new neurons and restore their lost learning and memory capabilities."

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In vitro cell culture findings could lead to novel interventions for schizophrenia

A study recently  has shown how using cultured cells from patients with psychotic disorders, such as schizophrenia, to investigate abnormalities in nerve connections in the brain could lead to new treatments. Strong correlations were observed between the findings in the cells in culture—grown outside the body in a controlled environment—and findings from brain imaging performed on the very same human participants. 

"The findings are important, because if the health of cells in culture reflects the health of the same cells in a human brain, we may be able to create a better model for studying psychotic disorders," said the study's senior author. He said such a model could give researchers a greater capacity to find genetic and biochemical targets in the brain. Using these targets, he said, "could enable us to develop novel and more effective interventions for psychotic disorders."

For their work, the team  drew on studies showing that altered pathways of brain development can be found across most cases of schizophrenia and that inaccurate connections and "leaks" in signaling between nerve cells are a feature of many psychotic disorders. A substance called myelin, produced by cells called oligodendrocytes, serves as a kind of insulation to prevent these leaks. In studies , myelin was measured and found to be reduced in the brain in patients with schizophrenias.

Based on this prior research, the researchers drew on a repository of cell lines they had obtained from patients with psychiatric disorders. These samples were reprogrammed from skin cells into brain-like cells in the laboratory. The reprogrammed cell lines, taken from both ill and healthy patients, produced nerve cells and support cells called glia, including oligodendrocytes, in laboratory cultures. Investigations into these cells revealed significant abnormalities in the development of oligodendrocytes grown from subjects with psychotic disorders.

The research also revealed a strong correlation between the number of oligodendrocytes in culture and the amount of myelin made by these cells in the brains of the same subjects who provided the cells. This finding, Cohen explained, "means that we can now study the causes of the abnormality of myelin that we have observed in living brain tissue in a laboratory setting."

For the researchers, the prospect of using lab cultures to examine differences in the brains of individuals with psychotic illnesses is "an exciting development." For example, the Prof. said, researchers have observed that not all genes and proteins necessary to make oligodendrocytes are affected in these cells, and they can now begin to identify exactly what genes and proteins are different in these cells. It would be impossible, he said, to do these detailed studies in living brain tissue.

Such studies, the researchers believe, could lead to better treatment approaches for individuals with psychotic conditions. "Using in vitro cell cultures to study these abnormalities could help us identify specific genetic and biochemical targets that might be addressed by novel drug treatments, cell transplantation, or other interventions," the Prof. said.

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