Neuroscientists fighting 'chemo brain' with help of sea snails

Since undergoing chemotherapy, Don Fredericks has spent every day searching for misplaced items or trying to finish a thought. Dubbed "chemo brain," the mysterious condition is now studied by three neuroscientists in Houston, Texas.

Chemo brain is a common term used by cancer survivors to describe thinking and memory problems that can occur after cancer treatment. Chemo brain can also be called chemo fog, chemotherapy-related cognitive impairment or cognitive dysfunction.

The new research is being conducted at the University of Texas Health Science Center (UTHealth) by Liu Rongyu, Ph.D, Zhang Yili, Ph.D -- both originally from China -- as well as UTHealth's Neuroscience Research Center Director John Byrne, Ph.D.

They are trying to find answers from sea snails, which have large memory neurons sharing similar memory functions with humans.

"We started two years ago with a drug called doxorubicin, or DOX, that according to the literature activates a protein called ERK critical for enhancing memory," Zhang said.

However, they found that DOX actually suppressed memory as it involves another protein called p38 MAPK.

Zhang said p38 MAPK and ERK have opposite effects on memory. ERK enhances memory by activating a protein called CREB1, while p38 always suppresses memory by activating a protein called CREB2.

"It might explain why not every patient has chemo brain after chemotherapy," Zhang said. "There might be a competition between ERK and p38 MAPK. Under some conditions, p38 MAPK wins. Under other conditions, ERK might win."

Byrne said that memory involves changes in the strength of the connections between nerve cells, and the team identified a specific biochemical process affected by a chemotherapeutic drug that interferes with that process.

"Now we found a mechanism in a snail, we will look to see if a similar mechanism is taking place in rats and mice," Byrne said.

"Eventually, we will look to see if a similar mechanism is taking place in humans and if we can find another drug that will counteract the effects of the doxorubicin," he said.

Byrne said the marine snail Aplysia californica was chosen for the first series of animal studies because it has a simple nervous system that contains about 10,000 nerve cells, the basic building blocks of the brain, in contrast to the 100 billion nerve cells in the human brain.

"If you can understand how it works in a simple nervous system, that will provide you with insight into how memory works in more complex animals," Byrne said.

However, the three team members agree that there is a long way to go. The additional steps include finding another drug to block the effects of DOX, conducting more animal testing, starting human test, and eventually securing an approval from the U.S. Food and Drug Administration for the therapy.

"If we know the mechanism for chemo brain we will find a way to treat it and cure it, and we're excited about that prospect," Liu said.