Stereo Investigator Contributes to University of Miami Study Showing Low Zinc Levels Associated With More Cell Deaths in Spinal Cord Injury
Spinal cord injuries can result in a range of physical disabilities from slight loss of motor function to major paralysis, but little is known about the mechanisms underlying the damage. Scientists affiliated with the Miami Project to Cure Paralysis at the University of Miami are gaining knowledge about how the nervous system responds to spinal cord injuries. Their latest study, published last month in the Journal of Neuroscience Research, suggests that post trauma cell death is associated with low zinc levels.
“The expression of functional NF-kB signaling resulted in a reduction in extracellular zinc levels, thereby inducing glutamate-induced cell death,” the authors say in their paper “Reduced Extracellular Zinc Levels Facilitate Glutamate-Mediated Oligodendrocyte Death After Trauma.”
Glutamate is a neurotransmitter that floods the injury site within an hour. In a process known as excitotoxicity, glutamate begins damaging cells. But since cell death doesn’t peak until four or twenty-four hours after injury, scientists speculated other factors might be involved. The researchers knew that zinc inhibits glutamate signaling, and that low levels of zinc don’t have the capacity to inhibit the deluge of glutamate that appears after spinal cord injury. They also knew that inhibiting the nuclear factor-kB transcription factor improves functional recovery and reduces white matter damage in a mouse model of SCI, so they blocked NF-kB activation in a transgenic mouse model, then conducted a series of in vitro tests on cultures derived from oligodendrocytes of both wild type mice and transgenic mice, which had, or had not experienced trauma to the spinal cord.
During the course of the study, the researchers used Stereo Investigator to quantify cells with positive staining for both TUNEL and an oligodendrocyte nuclear marker, so they could determine how many oligodendrocytes were undergoing cell death at certain time intervals.
According to the paper, the researchers gathered enough data to “lend strong support to [their] hypothesis that reducing extracellular zinc concentrations in the presence of glutamate potentiates cytotoxicity.”
“These studies demonstrate a novel role for zinc in regulating oligodendrocyte excitotoxicity and identify new therapeutic targets to prevent oligodendrocyte cell death in central nervous system trauma and disease.”
For more details about the study, visit www.ncbi.nlm.nih.gov.