Mouse Brain Study May Have Implications for Anxiety, PTSDWorking on a mouse brain, researchers have learned that nerves developed in a particular brain region can improve cognitive abilities.

In recent years, scientists have learned how to stimulate new nerve cell growth. The new research shows that neurons acquired in the brain’s hippocampus during adulthood can have a beneficial effect on cognition or mood.

Until now, studies have relied on interventions, such as exercise and enriched environments that affect numerous other processes in the brain in addition to increasing nerve development.

The research, led by René Hen, Ph.D., at Columbia University, appears in the Advance Online Publication of the journal Nature. Amar Sahay, Ph.D., a postdoctoral fellow, is the lead author on the study.

After boosting the number of neurons in the hippocampus, an area of the brain involved in memory and mood, the researchers tested the mice in both learning and mood-related tasks and looked for changes in behavior.

The researchers found specific effects on learning tasks that involve a process called pattern separation, which is the ability to distinguish between similar places, events and experiences.

“This process is crucial for learning because it enables us to know whether something is familiar or novel,” said Hen. “If it is familiar, you move on to the next bit of information; if it’s novel, you want to be able to recognize that it’s new and give it meaning.

“These mice, with just more adult-born neurons, and no other changes in the brain, basically learn better in tasks where they have to discriminate between similar contexts.”

Researchers believe that just as important as the ability to separate patterns is for learning, the ability to discriminate may also be important for anxiety disorders, including post-traumatic stress disorder (PTSD) and panic disorder.

Individuals with PTSD have a more generalized fear response, so that when they are placed in a situation that reminds them of even one aspect of their trauma, they frequently have a full fear response, say the researchers.

“I think a good example of this is someone who has developed PTSD as a result of 9/11. For them, the simple sight of an airplane or high tower may be enough to reawaken the initial traumatic episode and bring back the full aversive memory. Sometimes these generalizations become so pervasive that people basically don’t want to leave their home anymore because everything reminds them of the original event,” said Hen.

According ot the authors, the normal adaptive response is to separate similar events or experiences.

“Even though I may remember 9/11, when I see an airplane over NYC, I am able to recognize that it’s a different situation and process it accordingly, while someone in the same situation with PTSD may re-experience the traumatic memory of 9/11 and have a panic attack. So this may be one reason why stimulating neurogenesis to improve pattern separation may contribute to treatment of some of these anxiety disorders,” said Hen.

Improving pattern separation may be a helpful strategy to treat learning deficits seen in people with normal or pathological aging, such as Alzheimer’s disease.

In fact, there is already evidence that pattern separation declines during normal aging.

“This paper, as a consequence, may stimulate a whole area of research in humans to try to determine who in the population may have a pattern separation deficit, and whether it is restricted to the emotional domain, or is present even while performing tasks devoid of emotional salience. Once these studies are done in humans, it may be possible to treat these people with specifically targeted drugs or more personalized therapies,” said Dr. Hen.

The researchers say that the genetic strategy used to stimulate neurogenesis in their experiments can be mimicked pharmacologically, potentially leading to the development of new drugs to reverse pattern separation deficits. One such class of drugs the investigators are currently testing – BAX inhibitors – works by blocking cell death.

“These drugs are basically doing the same thing that we did with our genetic manipulation–namely, increasing the survival of the young neurons which normally undergo a process of cell death that eliminates at least half of these neurons. Now instead of dying, the neurons will go on to survive,” said Sahay.

Some BAX inhibitors have been developed for stroke research, where the goal has also been to prevent neurons from dying. The Columbia researchers plan to begin testing the BAX inhibitors in mice shortly. And if they produce cognitive benefits, the testing will be extended to clinical trials to determine if there’s also a beneficial effect in humans.

“I think we’re getting closer to harnessing neurogenesis to improve cognition and mood in humans. This research may also help explain a bit of a mystery in the field, which we still don’t understand, regarding how the hippocampus can be involved with both cognition – which is its classic function – and in mood and anxiety-related functions. Perhaps the fact that pattern separation affects both the cognitive and mood domains is the beginning of an answer to that paradox,” said Hen.

Source: Columbia University