What bank voles can teach us about prion disease transmission and neurodegeneration

This image shows accumulation of misfolded, toxic prion protein (brown staining) in the brain of a transgenic mouse expressing bank vole PrP and challenged with human variant Creutzfeldt-Jakob disease (vCJD) prions. Credit: Image courtesy of Dr. Joel Watts

When cannibals ate brains of people who died from prion disease, many of them fell ill with the fatal neurodegenerative disease as well. Likewise, when cows were fed protein contaminated with bovine prions, many of them developed mad cow disease. On the other hand, transmission of prions between species, for example from cows, sheep, or deer to humans, is -- fortunately -- inefficient, and only a small proportion of exposed recipients become sick within their lifetimes.

A study published on April 3rd in PLOS Pathogens takes a close look at one exception to this rule: bank voles appear to lack a species barrier for prion transmission, and their universal susceptibility turns out to be both informative and useful for the development of strategies to prevent prion transmission.
Prions are misfolded, toxic versions of a protein called PrP, which in its normal form is present in all mammalian species that have been examined. Toxic prions are "infectious"; they can induce existing, properly folded PrP proteins to convert into the disease-associated prion form. Prion diseases are rare, but they share features with more common neurodegenerative diseases like Alzheimer's disease.

Trying to understand the unusual susceptibility of bank voles to prions from other species, Stanley Prusiner, Joel Watts, Kurt Giles and colleagues, from the University of California in San Francisco, USA, first tested whether the susceptibility is an intrinsic property of the voles' PrP, or whether other factors present in these rodents make them vulnerable.

The scientists introduced into mice the gene that codes for the normal bank vole prion protein, thereby generating mice that express bank vole PrP, but not mouse PrP. When these mice get older, some of them spontaneously develop neurologic illness, but in the younger ones the bank vole PrP is in its normal, benign folded state. The scientists then exposed young mice to toxic misfolded prions from 8 different species, including human, cattle, elk, sheep, and hamster.

They found that all of these foreign-species prions can cause prion disease in the transgenic mice, and that the disease develops often more rapidly than it does in bank voles. The latter is likely because the transgenic mice express higher levels of bank vole PrP than are naturally present in the voles.

The results show that the universal susceptibility of bank voles to cross-species prion transmission is an intrinsic property of bank vole PrP. Because the transgenic mice develop prion disease rapidly, the scientists propose that the mice will be useful tools in studying the processes by which toxic prions "convert" healthy PrP and thereby destroy the brain. And because that process is similar across many neurodegenerative diseases, better understanding prion disease development might have broader implications.

Source:  PLOS

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Father-son research team discovers cheatgrass seeds survive wash cycle

Professor Hugh Lefcort and son Caleb examine the cheatgrass in Spokane, Washington. Credit: Gonzaga University

Not many sixth-graders can say they have been published in an academic journal, but Caleb Lefcort can cross that distinction off his list. Caleb got into a discussion with his father, Hugh Lefcort, professor of biology at Gonzaga University, as to whether the seed burrs from cheatgrass would survive the laundry cycle. Hugh believed the seeds would not survive. Instead of simply taking his father's word for it, Caleb -- who was in fourth grade at the time -- suggested the scientific method: an experiment.

The father and son duo set out to determine whether the seeds would survive the wash.
The experiment

Finding cheatgrass seeds was easy. Bromus tectorum (the scientific name for cheatgrass) is nearly ubiquitous in the Inland Northwest and has become an increasing concern throughout North America -- spreading rapidly through the western United States both through natural means and unintended ways, like getting stuck in people's socks and shoes.

"We hypothesized that laundering would impact water potential, and we, therefore, predicted that seeds would exhibit poorer germination and emergence after being laundered," said Hugh. "We also predicted that the effect of laundering would be stronger if bleach was used."

To collect the cheatgrass seeds, Hugh and Caleb walked through a nearby field wearing only socks on their feet. They divided the socks into three different treatments: 1. Not washed or dried; 2. Washed with detergent but not bleach and subsequently dried; and 3. Washed with detergent and bleach and then dried.

The socks that were to be laundered were divided into three different washing machines/detergent/dryer combinations:
1. A Whirlpool washing machine using All brand detergent and Whirlpool dryer;
2. A Samsung washer using Tide brand detergent and a General Electric dryer; and
3. A Maytag machine using Era brand detergent and a Maytag dryer.

Findings

The results of the experiment surprised both Hugh and Caleb.

"There was no significant effect of the different washing machines and their associated laundry detergents and dryers on the number of seeds that sprouted, nor did we find a significant effect of laundry treatments in the number of seeds that germinated," said Hugh.

There was, however, an effect on the seeds that were treated with bleach; they germinated at a slightly slower rate than the other seeds that were tested without bleach. The height of the plants that sprouted from these bleached seeds differed from the height of the plants that experienced the no-bleach-wash treatment.

The research that Hugh and Caleb conducted revealed that cheatgrass seeds and their germination processes are sturdy enough to survive the soaking, soap and agitation of washing machines, the heat of dryers, and often even bleach. Though they designed the study to make it difficult for cheatgrass seeds to germinate, they were surprised at how easily the treated seeds sprouted into plants. Government agencies may consider adding these findings to their public service announcements.

Caleb Lefcort is now a sixth-grader Moran Prairie Elementary School.

Source: Gonzaga University

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