When Stress Turns Toxic

It takes only three days for stress to harm the brain.

Posted Jul 29, 2016

By Emily Silber

Stress is a fact of life, an everyday companion for most. A little bit is actually good—it inspires action, even
excitement. But at some point stress turns from ally to adversary. A new study suggests that just three days of
stress can assault the structure of the brain in a way that quickly shows up as impaired memory.

Researchers from Trinity College Dublin and the National Centre for Biological Sciences in India subjected rats
to two hours of unremitting stress every day for 10 days and conducted periodic brain scans of the animals.
What is notable about the study, published this month in the journal Scientific Reports, is that the scientists got
to examine the progressive effects of stress on memory and cognition over time.

The animals were immobilized for two hours each day without access to food or water. A control group of
animals was allowed to live a normal lab rat’s life.

Stress targets the hippocampus, the part of the brain that stores basic memories, and causes it to shrink in size.
MRI scans of both groups of rats, taken on days three, seven, and 11, revealed that total hippocampal volume
was significantly lower in the stressed group after only three days of testing. And the shrinkage continued with
each stressful day, although the full impact was evident only after the end of the stress experiment. Disclaimer:
It is entirely possible that hippocampal loss starts even earlier—since the first MRI scan was not taken until day
three.

Behavioral tasks put to both groups throughout the study revealed how memory function was affected over
time. After day five the stressed animals began to exhibit significant problems in spatial memory, suggesting

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that there is a lag-time between hippocampal shrinkage and memory impairment. The more brain shrinkage, the
poorer an animal’s spatial memory. The stressed rodents also lost weight and exhibited anxiety-like behavior;
once released into an open field, they clung to the sidelines, reluctant to venture into open areas.

The body reacts to acute stressors by releasing stress hormones, which are essentially neurotoxic. The result is
not only death of existing cells but loss of neural plasticity and impairment of the ability to develop new
nervous tissue. The trifecta of loss diminishes the hippocampus with observable effects on spatial memory.

Is it possible that acute stress—the manageable bursts of stress that accent our days—turns toxic after only three
days or even less? Shane O’Mara, professor of experimental brain research at Trinity College Dublin and co-
author of the study, says that the conversion from acute to chronic stress occurs “when stress is repeated
frequently across multiple sleep-wake transitions and is inescapable or uncontrollable.”

But actually quantifying the metamorphosis is tricky. His guess is that “it takes three to four sleep-wake
transitions.” Sleep is a non-stressed state that gives brain and body a reprieve and a chance to repair. However,
if the stress is unremitting, sleep does not have a restorative function.

Under the assault, the hippocampus shrinks, followed in a few days by the effects on learning and memory, says
O’Mara. “There must be some degree of resilience and reserve present in these brain structures, and the stress
takes a little time to manifest itself as a behavioral change.”

For humans, equivalent memory damage would manifest as a loss of ability to position oneself in space and
time, says O’Mara—a very common symptom of Alzheimer’s disease. And it may be at least partly reversible
with exercise, known to stimulate neuron regeneration.

Unlike rats, we humans are also capable of cognitive strategies to disarm stress. We can change our perception
of it from a threat to a challenge, a process recently shown to actually diminish the release of stress hormones.