Uric acid is commonly associated with the excruciatingly painful joint disease known as gout, but it can also play a crucial role in the treatment of spinal cord injury and other central nervous system disorders, such as stroke, multiple sclerosis and Parkinson's disease, according to Rutgers' Bonnie Firestein.
Firestein, an associate professor of cell biology and neuroscience at Rutgers, The State University of New Jersey, and her laboratory team have reported their discovery in the Early View (online in advance of print) version of the journal Glia.
"In spinal cord injury, as well as stroke, two kinds of damage can occur," Firestein explained. "First there is the physical damage, but this is followed by secondary chemical damage to neurons [nerve cells] by compounds released in response to the trauma. We have found that uric acid can promote an early intervention step in combating this chemical damage through its action on astroglial cells."
Astroglial cells or astrocytes are specialized cells that support neuron function with nutrients and protective buffering.
In addition to the scientific achievement, the research study is a model for student involvement and education. Among the co-authors, postdoctoral associate Yangzhou Du is teaching Firestein more about astroglial cells, while he is learning about neurons from her. Christopher Chen was a Henry Rutgers Honors undergraduate student on the study, and Yuval Eisenberg, a laboratory technician; both now attend medical school. Another student, Chia-Yi Tseng is continuing her graduate studies in Firestein's laboratory.
Uric acid's affects on the health of neurons had been observed by other researchers, but the mechanics of how it confers protection has remained a mystery.
"It is interesting to note that people with gout never seem to develop multiple sclerosis," Firestein said. "In animal models of multiple sclerosis, the addition of uric acid reduces symptoms and improves prognosis. The same is true for one type of Parkinson's disease tested."
The Firestein team's breakthrough studies revealed that uric acid can stimulate astroglial cells to produce transporter proteins that carry harmful compounds away from neurons in jeopardy of chemical damage. This opens the door to identifying a unique drug target for new therapies.
Glutamate is a compound that under normal circumstances aids neurons in transmitting signals for cognitive functions in the brain, such as learning and memory. In the case of spinal cord injury or stroke where there is physical cell damage, however, an excess of glutamate is released and it accumulates around the remaining intact neurons, eventually choking them to death.
When Firestein's group added uric acid to a mixed culture of rat spinal cord neurons and astroglial cells, the production of the glutamate transporter EAAT-1 increased markedly. The challenge now is find the most effective strategy for increasing the production of the transporter, using drug therapies or other means.
Firestein said that a collaborative team of colleagues from Baylor College of Medicine and the University of Rochester Medical Center has devised one such strategy. With this team, Firestein will develop a line of stem cells that has been modified to generate astrocytes that produce large quantities of the EAAT-1 transporter. Adding these to an injury site, either alone or in combination with uric acid, holds great potential, she said.