Constant Stress Linked to Memory Loss

By Kristina Fiore, Staff Writer, MedPage Today
Published:  March 07, 2012
Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
                                   
Chronic stress may lead to memory problems by interfering with glutamate signaling in the prefrontal cortex, according to a study in mice.
Young male rats exposed to repeated stress had significant memory impairment and suppression of glutamate transmission in that brain region, Zhen Yan, PhD, of the State University of New York at Buffalo, and colleagues reported in Neuron.
The findings suggest that the prefrontal cortex "is a more sensitive area in response to repeated stress, especially during the adolescent period when this region is still undergoing significant development," the researchers wrote.
Chronic stress can impair executive functions, such as memory and attention, and has been shown to trigger maladaptive changes associated with stress-related mental disorders. The major stress hormone cortisol, for instance, has been linked with depression.
Some work has shown that stress hormones impair behaviors mediated by the prefrontal cortex, the brain region responsible for executive function.
Yet the underlying mechanisms remain elusive, the researchers said.
To delve deeper into those potential mechanisms, Yan and colleagues looked at glutamate receptor-mediated synaptic transmission, which has been suggested to be crucial for working memory, in mice.
They found that repeatedly exposing juvenile male rats to stress significantly impaired the temporal order recognition memory, a cognitive process controlled by the prefrontal cortex (P<0.01).
At the same time, they found that glutamatergic transmission in pyramidal neurons in the prefrontal cortex was significantly suppressed in those rats, although there was no loss of synaptic connections, they said.
Different downstream mechanisms have been identified in the effect of stress on glutamatergic signaling. Chronic stress reduces the expression of several receptors and proteins involved in glutamate transmission, including GluR1 and NR1 subunits (GluR1: 45% to 51% decrease, NR1: 55% to 63% decrease, P<0.01).
Chronic stress also reduced functional AMPAR and NMDAR current densities in prefrontal cortext neurons:

• AMPAR: 81.9 picoamperes/picofarad (pA/pF) for control versus 42.9 pA/pF for stressed (P<0.01)
• NMDAR: control: 93.3 pA/pF for control versus 40.4 pA/pF for stressed (P<0.01)

Yan and colleagues also found that blocking certain molecular processes prevented the loss of glutamatergic responses and recognition memory in the stressed mice.
"Our results suggest that repeated stress dampens prefrontal cortex glutamatergic transmission by facilitating glutamate receptor turnover, which causes the detrimental effect on ... cognitive processes," they wrote.
The findings may also help explain why stress responses can act as a trigger for many mental illnesses, they added.
"Since prefontal cortex dysfunction has been implicated in various stress-related mental disorders, delineating molecular mechanisms by which stress affects [this brain region] should be critical for understanding the role of stress in influencing the disease process," Yan said in a statement.

The researchers reported no conflicts of interest.
                
Primary source: Neuron
Source reference:  Yuen EY, et al "Repeated stress causes cognitive impairment by suppressing glutamate receptor expression and function in prefrontal cortex" Neuron 2012; DOI: 10.1016/j.neuron.2011.12.033.

http://www.medpagetoday.com/Psychiatry/AnxietyStress/31528

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