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A Whiff of Mad Cow
23 December 2008 (All day)
Talk about Dr. Jekyll and Mr. Hyde. Misfolded proteins known as prions cause mad cow disease and other fatal neurodegenerative illnesses. But in their properly folded form, the proteins may be important to survival, helping mice and other animals keep their sniffing skills sharp, new research shows.
Prions get the bad reputation--and the lion's share of research attention--but interest in the normal form of prion proteins is increasing. Brain tissue is particularly high in these proteins, and a growing body of research has shown that they help neurons conduct copper and may even protect them from destruction by rogue chemicals in the body. But no one had pegged prion proteins to a particular neurological function such as sight or smell.
That's changed, thanks to an intriguing finding by electrophysiologist Stuart Firestein of Columbia University. Firestein and colleagues were studying the sense of smell in mice when they noticed high levels of normal prion protein (PrPc) in the cells that make up the animals' olfactory systems. Wondering whether the protein might play a role in this sense, the researchers hid bits of peanut butter cookies in the shredded bedding of a cage. They then timed how long it took both normal mice and rodents genetically engineered to not make PrPc to sniff out the snack. Normal mice spent an average of 73 seconds searching for the treat before they found it, three times faster than their PrPc-free counterparts. Six of the 20 PrPc-free mice never found the cookie at all, the team reports this week in Nature Neuroscience.
The genetically engineered mice performed worse on other measures of smell acuity as well. For example, when the researchers piped the scent of peanut butter into the cage, normal mice spent less time nosing in the direction of the smell as they became used to it. But their sniffers would perk up again when a new scent like vanilla or honey was introduced. The PrPc-free mice acted no differently when presented with a new scent, suggesting they couldn't discriminate between familiar and novel smells. The performance of the genetically modified mice improved once the researchers turned on their PrPc-making genes.
The complete inability to smell, called anosmia, can be deadly to animals, because they rely on scent to find food. But the PrPc-free mice showed good appetites and appeared healthy overall, the team reports. This suggests that the PrPc protein alone doesn't determine whether an animal has a sense of smell. Instead, animals without prion protein may not detect odors as intensely or be able to distinguish between different smells, says Columbia University electrophysiologist and team member Matthew Valley. "It's like the animals have gone from 20/20 vision to 20/100 vision."
Showing that the normal prion protein plays a role in an animal's sense of smell is an important contribution, because it pegs the protein to an actual neurophysiological process, says Gerald Zamponi, a molecular neurophysiologist at the University of Calgary in Canada. "This is the first description of true change in a physiological response" due to this protein, he says, whose healthy function has been very tough to pin down.