Mouse study suggests that survivors of severe heart attacks may have problems learning certain tasks

Sep 29 2004

A new study in mice suggests that survivors of severe heart attacks may have a difficult time with some learning tasks.

Cardiac arrest can take a particularly harsh toll on the hippocampus, the area of the brain that plays a role in memory and navigation. A lack of oxygen during a severe attack – one where the victim stops breathing – can either kill or seriously damage neurons, the primary cells of the nervous system.

The neurons that do survive a heart attack may undergo major structural changes that can affect learning, memory and other behaviors, said Courtney DeVries, the study's lead author and an assistant professor of psychology and neuroscience at Ohio State University.

Indeed, in the current study the mice that had had a heart attack had far more difficulty learning a new spatial task than did healthy mice.

"The neurons that survived a heart attack looked very different from normal, healthy neurons," DeVries said. "These changes could be part of the physiological basis for memory deficits and other behavioral changes that patients often report following an attack."

The study appears in a recent issue of the European Journal of Neuroscience.

Mice were put into two groups – one group underwent surgically induced heart attacks, while the other group, the control group, underwent the same surgical procedure minus the attack. Mice in the heart attack group spent about eight minutes in cardiac arrest – enough time to stop the flow of oxygen to the brain.

Prior to surgery, the animals navigated the Morris water maze – a task that requires finding an escape platform hidden just below the surface of opaque water. Mice underwent three trials a day for eight days to acclimate them to the maze. Each mouse had 60 seconds to swim around the circular, two-meter-wide tank to find the platform. The researchers tracked how long it took each mouse to reach the platform, as well as how fast and how many meters the animal swam during its search.

By the end of this training phase, each mouse had learned where the platform was and could swim to it directly regardless of where the mouse was placed in the tank.

All of the mice were reintroduced to the maze about a week after surgery. The researchers left the platform in the same place as it had been prior to the surgeries because they wanted to know if the animals had remembered where the platform was. None of the mice had problems locating the platform.

That changed, however, when the researchers moved the platform from its original position to the opposite side of the tank.

"While the mice in the cardiac arrest group had no trouble locating the platform in its original position, their ability to learn the platform's new location was hindered," DeVries said.

The animals were tested three times a day for three days. By the last day of these tests, the mice in the cardiac arrest group swam an average of two meters more than did the control mice in their search for the platform.

"The mice now had to learn a new strategy for finding the platform, and the mice in the cardiac arrest group weren't able to adapt," DeVries said.

The researchers wanted to see how cardiac arrest had affected neurons in the mouse hippocampus. They looked specifically at dendritic spines – projections from neurons involved in sending signal throughout the central nervous system and the body.

There was an overall 18 percent decrease in dendritic spine density in the hippocampus in the cardiac arrest mice compared to the control mice, a finding that represents a functionally significant loss, DeVries said.

"Similar decreases in dendritic spine density have been associated with altered behavioral outcomes, such as changes in performance in spatial memory tasks," she said. "This decrease in the number of dendritic spines may have had a direct effect on the performance of the cardiac arrest group.

"Most people who survive a heart attack are left with perfectly functional neurons, along with ones that are clearly injured," she continued. "The long-term goal is to figure out how to alter the brain's environment to bring those damaged neurons back to full function. We can start by looking at the cells' immediate environment to see what causes that alteration, and possibly reverse that."

DeVries and her colleagues are continuing this work by looking at how different types of social interactions influence the number and health of neurons that survive a heart attack.

"We hope that positive social interaction will actually improve the animals' recovery from cardiac arrest," DeVries said.

She conducted the study with Gretchen Neigh and Erica Glasper, both graduate students in neuroscience and psychology at Ohio State; Julia Kofler and Richard Traystman, both with Oregon Health and Science University; and with Ronald Mervis and Adam Bachstetter, both with NeuroStructural Research Laboratories in Tampa.