University of Florida researchers may have discovered why some brain cells necessary for healthy memory can survive old age or disease, while similar cells hardly a hairsbreadth away die.
The discovery, published online ahead of print in the Nature publication Cell Death & Differentiation, could help scientists understand and find solutions for age-related memory loss.
Scientists with UF's Evelyn F. and William L. McKnight Brain Institute describe how they analyzed two neighboring regions of a tiny brain structure called the hippocampus in rats of varying ages. They found that a recently discovered enzyme known as PHLPP, pronounced "flip," may be silencing a vital cell-survival protein in the region where neurons are most susceptible to damage and death.
"The question is why does one set of brain cells live and another set die when they are only millimeters apart in the same small brain structure?" said Travis C. Jackson, a graduate student working with Thomas C. Foster, Ph.D., the Evelyn F. McKnight chair for research on aging and memory at UF. "We looked at an important signaling pathway that tells cells to stay alive or die, and the enzymes that regulate that pathway. Implicated in all this is a new protein that before a couple of years ago no one actually knew much about."
The scientists focused on the hippocampus, an anatomical region shaped something like a curved kidney bean in mammals. The structure is widely believed to be central to the formation of memories, as well as an important component of motivation and emotions. A portion of it is known to be especially vulnerable to decreased cerebral blood flow, which can occur because of stroke or circulatory problems. The same area is also one of the earliest brain regions to show pathology associated with Alzheimer's disease.
Researchers studied both regions for signs of AKT, a protein that when activated, actually hinders many naturally occurring inducers of cell death. They found activated AKT was scarce among the cells that are vulnerable to damage and death and more abundant within the hardier cells.
The next step was to figure out what was turning off AKT in the vulnerable cells, which led scientists to PHLPP1, a recently discovered enzyme that is believed to be a natural tumor suppressor. Where PHLPP1 levels were high - which corresponded to the area with the vulnerable cell population - AKT activation was far less robust.