AN INFECTIOUS IDEA -- A VIRUS-LIKE PROTEIN MAY BE CRUCIAL TO LEARNING AND MEMORY

We've all heard the phrase, "an infectious idea." It turns out that this may not just be a metaphor--new research has revealed that a virus-like protein in all of our brains may be vital for learning and memory.

"If it looks like a duck and quacks like a duck," the saying goes, "it probably is a duck." So, no matter how surprising it is, finding a crucial protein in the brain that looks like a virus and acts like a virus raises the intriguing possibility that our ability to learn and remember may stem from a chance infection of some ancestral four-legged creature by a retrovirus 350 to 400 million years ago.

The protein in question is called Arc. It's found in animals as different as flies, mice and humans. It's been known for some time that Arc is important for learning and memory. Mice lacking Arc forget what they've learned within 24 hours, and lack the kind of brain plasticity that lets young animals, most notably human children, soak up new information quickly and easily. Arc continues to be important for learning and memory throughout life, and impaired Arc functioning is associated with autism, amnesia and Alzheimer's disease.

Arc (long purple proteins inside the perimeter of the vesicle) can encapsulate and deliver its own genetic material to brain cells (light green branching blobs) in a manner similar to the way in which viruses infect host cells.  

Credit: Jacobo Lopez, Yi-Chu Su, Hugo Vaca

Jason Shepherd, a neuroscientist at the University of Utah, and his colleagues first suspected that something was different about Arc when they found that the protein self-assembles into structures called capsids that look like a lunar lander or the HIV retrovirus. Intrigued, they found that not only can the Arc capsid jump from cell to cell like a virus, it also transfers its own genetic material in the form of messenger RNA into the new cell.

Learning takes place when interconnected brain cells are activated at the same time. Intriguingly, the researchers found that when neurons "infected" by Arc are activated, they release newly minted Arc capsids. This suggests that the transfer of this virus-lilke protein from cell to cell may be a previously unknown and unsuspected mechanism for learning and memory.

Neuron expressing Arc and transferring it to other neurons

Credit: Elissa Pastuzyn 

“We went into this line of research knowing that Arc was special in many ways," says the study’s lead author, postdoctoral fellow Elissa Pastuzyn. "But when we discovered that Arc was able to mediate cell-to-cell transport of RNA, we were floored. No other non-viral protein that we know of acts in this way.”

Geneticists have been able to trace back the history of the Arc proteins found in all mammals. Sometime between 350 and 400 million years ago, a primitive four-limbed creature, or tetrapod, was infected by a retrovirus that left some of its genetic material in the animal's DNA. That chance addition to the mammalian genetic code has apparently proven extremely useful, perhaps laying the groundwork for the success of our mammalian ancestors, and even for our remarkable capacity for learning and remembering.

REA

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You can read more about this research at this URL.

The scientific article describing this research can be found in Cell, January 11, 2018.

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YOU KNOW THOSE BRAIN-TRAINING EXERCISES--THEY MAY ACTUALLY MAKE A DIFFERENCE

If you type "brain training exercises" or "brain training games" into a search engine, you'll get millions of hits. Companies offering games and exercise promising to ward off failing memory, loss of concentration and other signs of cognitive decline have become big business. These exercises have also become controversial, with some studies and experts highly critical of their usefulness.

Brain-training research, Brain and Mind Centre/Credit: University of Sydney

A new study published today in the American Journal of Psychiatry can shed some light on this issue. Researchers at the Brain and Mind Centre at the University of Sydney, in Australia, reviewed more than twenty years worth of research on the effects of computerized cognitive training (CCT). They selected only randomized clinical studies, and used the statistical technique of meta-analysis to combine the results. 

Their findings are surprisingly clear--for people with mild cognitive impairment, structured brain training can boost general thinking skills, attention, working or short-term memory, verbal long-term memory, learning and mood. 

Mild cognitive impairment, or MCI, represents a kind of middle ground between the kinds of memory and other cognitive problems that occur with normal ageing and the more severe changes seen in Alzheimer's disease and other full-blown dementias. Typically about 10 percent of people diagnosed with MCI develop Alzheimer's or another form of dementia within a year.

In general, the kinds of computerized games and challenges studied did not help after people had already been diagnosed with dementia. Intriguingly, however, three studies that used more immersive technology such as Nintendo's Wii or virtual reality did show positive results even then--a lead well worth following.

Although emphasizing that further research is needed to see if the clear improvements caused by these cognitive exercise programs delay or perhaps in some cases prevent dementia, the researchers are encouraged. "Our research shows that brain training can maintain or even improve cognitive skills among older people at very high risk of cognitive decline," says neuroscientist Amit Lampit, who lead the study. "and it's an inexpensive and safe treatment."

With recent research also showing that structured physical exercises can also improve cognitive functioning in people with MCI (see my blog entry for 10/25/16), we can see the outline of safe and inexpensive interventions that may keep people's brains healthy and functioning well even as they age.