Fascinating research findings are reported by the National Institute of Allergy and Infectious Diseases (NIAID):
Scientists for the first time have watched agents of brain-wasting diseases, called transmissible spongiform encephalopathies (TSE), as they invade a nerve cell and then travel along wire-like circuits to points of contact with other cells. These findings will help scientists better understand TSE diseases and may lead to ways to prevent or minimize their effects. TSE, or prion, diseases include scrapie in sheep and goats; chronic wasting disease in deer and elk; mad cow disease in cattle; and Creutzfeldt-Jacob disease in humans.
Under the direction of Byron Caughey, Ph.D., at the Rocky Mountain Laboratories (RML), and Marco Prado, Ph.D., at the University of Minas Gerais in Belo Horizonte, Brazil, the team performed the research in laboratory cultures using a rodent-adapted form of scrapie protein and cells taken from the central nervous system of mouse and hamster brains. The proteins were first “branded” with fluorescent dyes so they could be easily tracked.
The work also revealed that a similar trafficking process might occur with the key plaque-forming protein in Alzheimer’s disease, which is not a TSE but a different type of degenerative brain disease, according to Gerald Baron, Ph.D., one of the lead RML researchers…
Dr. Baron says researchers have tracked infectious prion protein moving through other parts of animal bodies up to the brain, but no one had ever tracked the protein movement within animal brain cells. One of the most difficult aspects of the experiment, he says, was finding a way to fluorescently tag the TSE prion proteins without altering them–while still allowing researchers to identify the prions as they penetrated the cells and spread within the long projections that nerve cells develop to send signals to other nerve cells.
“This was difficult from a technical aspect because the scrapie pathogen is largely a corrupted form of a host cell protein,” Dr. Baron said. “It can be hard to detect the corrupted prion protein in living infected cells and distinguish it from its normal counterpart.”
He explains that once researchers learned how to mark the prion proteins, they added them to a culture of nerve cells and then began watching and taking photo images with a confocal microscope. Confocal microscopy uses laser light to scan many thin sections of a fluorescent sample, resulting in a clean three-dimensional image. The painstaking job of analyzing and deciphering about 1,000 different images primarily belonged to Dr. Magalhaes–who filled a file cabinet drawer with CDs containing microscopic images. The effort resulted in striking photos that, when put into a video format, show prion protein moving within cells, then along narrow cellular projections called neurites and ultimately into close proximity with adjacent cells.
The press release by NIAID…
