In the December 9 issue of Cell, a research team led by Mauro Costa-Mattioli report on how a key component of the immune system may also play a central role in the brain’s ability to form memories.
The molecule in question is the enzyme “protein kinase RNA-activated” or PKR for short. PKR is well-known to biomedical researchers. It is found in nearly all vertebrates and helps fight viral infections.
What was unknown is how PKR plays a pivotal role in regulating how the brain forms memories. Using mice, Costa-Mattioli’s team found that PKR actually slows down the brain’s ability to form memories. By blocking the production of PKR in mice, Costa-Mattioli’s team was able to produce mice with enhanced memory.
“The molecule PKR (the double-stranded RNA-activated protein kinase) was originally described as a sensor of viral infections, but its function in the brain was totally unknown," said Costa-Mattioli in a press release issued by Baylor Medical College.
The researchers used two methods to block PKR. They produced mice that were genetically modified so they couldn’t produce PKR. But they also used a drug that inhibits the production of PKR. In both cases, memory capacity was enhanced.
How does PKR act in the brain? Apparently by interacting with another key molecule, interferon-γ or IFN-γ, which is also best known for its role in the immune system. Researchers believe that in the brain, PKR and IFN-γ interact, keeping each other in balance. Suppressing PKR seems to increase the role of IFN-γ and the activity of the brain, particularly the neurons that are creating long-term memories.
“These data are totally unexpected, and show that two molecules classically known to play a role in viral infection and the immune response regulate the kind of brain activity that leads to the formation of long-term memory in the adult brain,” said Costa-Mattioli.
What is perhaps most startling about the report is that a drug that inhibits PKR enhances memory in mice. “It is indeed quite amazing that we can also enhance both memory and brain activity with a drug that specifically targets PKR,” according to Costa-Mattioli.
If a drug enhances memory capacity in mice, could it work in humans? That’s a big jump, one that will take much more research before anything is even tested in human beings. But researchers suggest that this is possible and worth exploring. Costa-Mattioli said, "More investigation is undoubtedly necessary to translate these findings to effective therapies but we would be delighted if our scientific studies were to contribute in some way to this ultimate goal."
“Our identity and uniqueness is made up of our memories," Costa-Mattioli said. "This molecule could hold the key to how we can keep our memories longer, but also how we create new ones.”
Will this provide a new strategy in dealing with diseases that rob us of our old memories and of our capacity to create new ones? Given the stakes, research will explore these possibilities.
If the research is applicable to human beings (and why not?) and if it provides a new path to preventing or delaying dementia, it will also open new ways to think about the enhancement of human cognition. The mice in the study were not suffering from any memory loss, but the speed at which they were able to learn a new task was enhanced nearly four-fold.
Given the wide-spread interest in cognitive enhancement, especially on university campuses and among transhumanists, we should expect to hear more about how inhibiting PKR just may make you smarter.
The article, "Suppression of PKR Promotes Network Excitability and Enhanced Cognition by Interferon-γ-Mediated Disinhibition,” appears in the December 9 issue of Cell.