Studies show even short periods of stress take toll on brain cells, a clue to post-traumatic stress disorder

Thursday, January 17th 2002, 12:00 am

By: News On 6

WASHINGTON (AP) _ Even relatively short periods of stress may cause changes that leave brain cells hypersensitive for weeks, report Israeli scientists trying to uncover the molecular root of post-traumatic stress disorder.

The experiments were with mice, and it's far from clear if human brain cells react the same way. But the research is generating interest among scientists struggling anew to unravel traumatic stress in the aftermath of terrorism.

``It's a tantalizing new lead,'' said Rockefeller University professor Bruce McEwen, who researches stress effects on the brain.

Anyone who has ever experienced trauma knows such experiences can leave you nervous, easily startled. It's one way the body protects itself from future harm, by learning from a bad experience. But in some people, this protective mechanism goes too far, leading to high anxiety, nightmares and flashbacks known as post-traumatic stress disorder.

No one knows just what happens to switch a normal stress response to an abnormal, hyper response.

But in Friday's edition of the journal Science, Hermona Soreq and colleagues at Hebrew University argue a key player is a brain protein called acetylcholinesterase, or AChE, that is important in helping messages jump from one neuron to the next.

Soreq exposed mouse brain cells to AChE-affecting chemicals, including the stress hormone cortisol, and examined the brain tissue of mice stressed in such ways as forcing them to swim.

Within minutes, relatively short periods of stress caused the mice to produce a usually rare, abnormal version of AChE that doesn't provide the same help in neuronal signaling.

That somehow left the mice's neurons hypersensitive. Brain scans found higher levels of electrical activity that lasted for weeks, a lengthy effect Soreq called surprising.

Soreq also works for an Israeli drug company attempting to create an AChE-targeting treatment for traumatic stress. One of the mouse cell studies suggested a chemical called EN101 could be a candidate for further study.

Sometimes, ``we need stress responses. ... We need to be more alert, we need neurons to be active when the situation calls for that,'' Soreq said. But, ``our findings show that traumatic experiences as well as certain chemicals do have long-lasting effects, and that repeated stress may cause cumulative effects.''

Why study AChE? Soreq cites similarities in symptoms between patients with post-traumatic stress disorder and people poisoned by agricultural chemicals that target the cholinergic system. That system is involved in how the brain stays vigilant. Also, AChE interactions with other brain chemicals have been associated with memory and behavior.

But it's far from the only theory behind post-traumatic stress disorder, cautioned Rockefeller's McEwen. On Jan. 29, he is hosting a special lecture in New York City for people worried about the effects of the Sept. 11 terrorist attack, where scientists from five universities will put into laymen's terms all that is known about stressing the brain.

Based on a study that blocking certain cell receptors inhibits the formation of bad memories, some researchers are exploring whether beta-blocking drugs might prove stress-protective, McEwen said.

Other research shows the actual brain circuitry in a region called the amygdala changes after an animal is stressed, findings generating intense interest.

Even newer studies suggest trauma victims whose bodies produced less of the stress-related hormone cortisol in the aftermath were more likely to develop post-traumatic stress disorder.

The disorder ``is a very complicated phenomenon in which various hormones in the body and various systems in the brain may all be involved,'' McEwen notes. While Soreq's abnormal AChE may indeed play a role, ``it's far from clear exactly how and where.''

But regardless of what causes post-traumatic stress, the good news is ``the brain is very resilient. Many of these changes are not irreversible,'' he said.