Synthetic neurons may reveal clues to herpes infection
OREANDA-NEWS. Researchers have optimized a new method to create synthetic neurons, neuron-like cells created from a readily available cell line.
They also used these cells to investigate a core enzyme involved in the synthesis of purines—a component of DNA that is involved in many other cellular and metabolic processes—and how the enzyme might change during infection by herpes simplex virus.
An early version of the paper describing the enzyme appears in the Journal of Neurochemistry, and a paper describing the neuron-like cells appears in the Journal of Virology.
“These newly developed neuron-like cells allowed us to investigate purine formation in a specialized cell type for the first time,” says Moriah Szpara, assistant professor of biochemistry and molecular biology at Penn State and senior author of both papers.
“We were interested in neurons because they require a lot of energy and therefore need to produce purines efficiently. We were also curious how the synthesis process might be affected by infection with herpes simplex virus, an energetically demanding virus that takes up residence in neurons,” Szpara says.
When demand for purines is high in a cell, a complex composed of many enzymes called the purinosome forms to enable faster production of these important chemicals.
The researchers investigated an enzyme called FGAMS, a core component of the purinosome. To better understand the role of FGAMS in purine production, they looked at where and how much of the enzyme is expressed in rodent brain slices, rodent neurons, human non-neuronal cells, and the human neuron-like cells cultivated with the new technique.
“Studying human neurons has been challenging because we haven’t had a good laboratory model to study them,” says Colleen Mangold, a postdoctoral researcher at Penn State and an author of both studies.
“We can use neurons from rodents or chick embryos, but they don’t give us the same information as human cells. Most studies require large numbers of cells, so we developed a method to take a commonly available cell line and shape it into cells that look and act like neurons. This new method will allow us to start asking the backlog of questions we have about neurons, like how purines are synthesized in the brain,” Mangold says.
In the neuron-like cells and in rodent neurons and brain slices, FGAMS was expressed in a number of locations throughout the neuron, including near mitochondria and microtubules. Because FGAMS is also found near these structures in non-neuronal cells, the researchers suspect that purinosome formation may be conserved across different cell types.