The Good Side of Brain Manglers

If normal prions facilitate communication between the cells of an embryo, it’s likely they also aid in the dialogue between adult cells. That’s because similar processes in adults also require cells to “talk” to one another, such as when neurons signal to muscles to move, or when skin cells replicate. “Every time you move your arms, there is a neuron making contact with a muscle, and [skin] cells also need to communicate with themselves to maintain tightness,” says Málaga-Trillo. “Cells are talking to each other, saying ‘we need to replicate.’” Losing the ability to make contact between cells can result in neurological disorders and other diseases.

Still, some researchers remain cautious about drawing parallels between the fish in the study and humans. Although the study links normal prions with zebrafish development, the genetic makeup of these proteins may differ between zebrafish and humans, and their function in the body could vary as well. “I’m not necessarily sure the fish gene [for normal prions] is the same as the mouse gene,” says Walker Jackson, who researches prions at the Massachusetts Institute of Technology in Cambridge, Mass. The gene sequences of the two animals are quite different.

Still, the zebrafish study isn’t the only one to show that normal prions may be vital for communication between cells. Others have shown that these proteins may also help brain cells, or neurons, talk to each other. Neurons connect head-to-toe, dendrite-to-axon, like a relay team, one passing an electrical signal to another. Normal prions perch on the ends of neurons, straddling the synapse, the junction between the two brain cells. Scientists postulate that normal prion proteins act as go-betweens among these brain cells, and that they may even help form memories by “talking to” similar proteins poised on adjacent neurons. “When it interacts with itself, it can mediate interaction between those cells,” says Sandra Encalada, a prion researcher at the University of California, San Diego.

The way normal prions pass messages between cells may explain why they also appear to play a role in our sense of smell. A study led by Firestein, the Columbia University researcher, linked normal prions to mice’s sense of smell, and the absence of these proteins to defective olfaction. (Firestein, while not originally a prion researcher, has researched our sense of smell for nearly 15 years). Our ability to smell, known as the olfactory sense, is enabled by the olfactory bulb, a slender, tubelike projection that sits below the brain and directly above the nasal cavity. It sends signals to the brain when scent molecules enter the nose. When you take a whiff of a hot cup of coffee, for example, aromatic molecules rise from the liquid, attaching themselves to tiny sensors in the nose, which pass the signal to your brain through a network of neurons and specialized sensory organs.

When Firestein and his research group were examining the types of proteins found in the olfactory bulb under an electron microscope, they were surprised to find a large number of normal prions in the organ. “It looked very interesting to us,” says Firestein, whose wavy white hair and neat navy blue tie belie his propensity for casually peppering his speech with swear words. “It got us started on the prion thing.”

So Firestein decided to investigate why there were normal prions in the olfactory bulb, and whether they are necessary to a mouse’s sense of smell. “We started looking to see if we could see an olfactory deficit [in the prion-free mice] to see if there was some mucking up of that,” says Firestein.

To test for the importance of prions in the animals’ sense of smell, the researchers hid a Nutter-Butter cookie in a maze and timed how long it took for the mice that lacked prions to find it. “The prion-free mice failed the test pretty miserably. They’d sort of sniff around, but rarely got to the cookie,” says Firestein. “Most of the mice would wander around the cage and sniff, but just didn’t get the cookie.”

What’s more, normal mice improved the speed at which they could get the cookie after each trial. The few prion-free mice that happened to find the Nutter Butter on their first try, however, did not find the cookie any faster the second time, indicating that the mouse’s sense of smell was somehow impaired in the absence of prion proteins. But what puzzles Firestein and his team is that the mice smelled well enough to perform tasks that are crucial to survive and reproduce, Firestein says. “Without a sense of smell, mice don’t mate, and they don’t suckle,” he says. “There were clearly deficits in the olfactory behavior, but these animals could smell.”