This is a recurring column on early-stage research in animals or other laboratory models that has not entered the clinic yet but could have implications for future research and development of human medicines.
Scientists have discovered a cell signaling pathway that may interfere with protein production in the brain, causing learning and memory problems in people born with Down syndrome.
In a study funded by the U.S. National Institutes of Health's National Institute of Neurological Disorders and Stroke, the National Human Genome Research Institute and the U.S. National Cancer Institute, researchers looked at how the most common cause of intellectual disability — caused by inheriting an extra copy of chromosome 21 — alters protein levels in the brain.
A cell signaling pathway can interfere with protein production in the brain, causing memory problems in people born with Down syndrome, a study in mice showed.
Researchers led by Mauro Costa-Mattioli from Baylor College of Medicine and Peter Walter from the University of California, San Francisco, focused on integrated stress response, or ISR, which contributes to the reduction of protein production in the cell. Using a mouse model of Down syndrome called Ts65Dn, in addition to brain tissue and cells from people with Down syndrome, they found that protein production was 40% lower in the brains of the Ts65Dn.
Furthermore, the ISR was persistently active in the hippocampus — a region of the brain which plays a central role in learning and memory formation — of the Ts65Dn mice, driven by an enzyme called PKR. When PKR was inhibited, either genetically or with drugs, the mice had normal protein production levels and were able to perform on a par with normal mice on standard memory and behavior tests.
"More than 10 years ago we discovered that the ISR serves as a molecular switch for the protein synthesis needed for long-term memory formation," Costa-Mattioli said. "In this study, we found that the switch is off in Down syndrome. More importantly, turning the switch back on in these mice reverses their long-term memory deficits."
They also discovered increased ISR activity in samples taken from brains of people with Down syndrome. Further experiments revealed that blocking PKR in the brains of Down syndrome mice improved communication between nerve cells — a process required for memory formation.
The results were published Nov. 15 in Science.
New use for pain drug
Gabapentin, a drug commonly prescribed for neuropathic pain, partial seizures and epilepsy could help restore upper limb function after spinal cord injury, according to research on mice undertaken at The Ohio State University.
In the study, mice treated with gabapentin regained roughly 60% of forelimb function in a skilled walking test, compared to the restoration of around 30% in mice on placebo. The regained function in mice occurred after four months of treatment, which is the equivalent of about nine years in adult humans.
"I think there's enough evidence here to reconsider how we use this drug in the clinic," said senior author Andrea Tedeschi, who is assistant professor of neuroscience at the university. "The implication of our finding may also impact other neurological conditions such as brain injury and stroke."
Results of the study were published in the Journal of Clinical Investigation.
Cancer risk from low-dose radiation
Low doses of radiation equivalent to three CT scans give cancer-capable cells a competitive advantage over normal cells in healthy tissue, scientists at the U.K.'s Wellcome Sanger Institute and the University of Cambridge found.
Low doses of radiation give cancer-capable cells a competitive advantage over normal cells in healthy tissue, researchers found.
Looking at the effects of low doses of radiation in the oesophagus of mice, the researchers found that the number of cells with mutations in p53, a well-known genetic change associated with cancer, increased. However, giving the mice an antioxidant before radiation promoted the growth of healthy cells, which outcompeted and replaced the p53 mutant cells.
Researchers advise that this risk should be considered in assessing radiation safety. The study also offers the possibility of developing non-toxic preventative measures to cut the risk of developing cancer by bolstering healthy cells to outmaneuver and eradicate cancer cells.
"Our bodies are the set of 'Game of Clones' — a continuous battle for space between normal and mutant cells," said David Fernandez-Antoran, first author from the Wellcome Sanger Institute. "We show that even low doses of radiation, similar to three CT scans' worth, can weigh the odds in favor of cancer-capable mutant cells. We've uncovered an additional potential cancer risk as a result of radiation that needs to be recognized."
Results of the study were published in Cell Stem Cell.
Editor's Note: S&P Global Market Intelligence will not be publishing Of Mice Not Men on Dec. 25 and Jan. 1. Publication resumes Jan. 8.