Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study in Mice Raises Question: Could PTSD Involve Immune Cell Response to Stress?

21.02.2014
After chronic stress, primed immune cells in spleen lead to excessive reaction to later event

Chronic stress that produces inflammation and anxiety in mice appears to prime their immune systems for a prolonged fight, causing the animals to have an excessive reaction to a single acute stressor weeks later, new research suggests.

After the mice recovered from the effects of chronic stress, a single stressful event 24 days later quickly returned them to a chronically stressed state in biological and behavioral terms. Mice that had not experienced the chronic stress were unaffected by the single acute stressor.

The study further showed that immune cells called to action as a result of chronic stress ended up on standby in the animals’ spleens and were launched from that organ to respond to the later stressor.

Mice without spleens did not experience the same reactivation with the second stressor, signifying the spleen’s role as a reservoir for primed immune cells to remain until they’re activated in response to another stressor.

The excessive immune response and anxiety initiated by a brief stressor mimic symptoms of post-traumatic stress disorder.

The Ohio State University scientists are cautious about extending their findings to humans. But they say their decade of work with this model of stress suggests that the immune system has a significant role in affecting behavior. And they are the first to study this re-establishment of anxiety in animals with a later acute stressor.

“No one else has done a study of this length to see what happens to recovered animals if we subject them again to stress,” said Jonathan Godbout, a lead author of the study and associate professor of neuroscience at Ohio State. “That retriggering is a component of post-traumatic stress. The previously stressed mice are living a normal rodent life, and then this acute stress brings everything back. Animals that have never been exposed to stress before were unaffected by that one event – it didn’t change behavioral or physiological properties.”

The research is published online in the journal Biological Psychiatry.

These scientists previously determined that in mice with chronic stress, cells from the immune system were recruited to the brain and promoted symptoms of anxiety. The findings identified a subset of immune cells, called monocytes, that could be targeted by drugs for treatment of mood disorders – including, potentially, the recurrent anxiety initiated by stress that is a characteristic of PTSD.

The research reveals new ways of thinking about the cellular mechanisms behind the effects of stress, identifying two-way communication from the central nervous system to the periphery – the rest of the body – and back to the central nervous system that ultimately influences behavior.

“We haven’t proffered that there is a cellular component to PTSD, but there very well might be. And it’s very possible that it sits in the periphery as we’ve been describing in the mouse,” said John Sheridan, senior author of the study, professor of oral biology and associate director of Ohio State’s Institute for Behavioral Medicine Research.

In this model of stress, male mice living together are given time to establish a hierarchy, and then an aggressive male is added to the group for two hours at a time. The resident mice are repeatedly defeated, and this social defeat over six days leads to an inflammatory immune response and anxiety-like behavior.

This kind of stress triggers the sympathetic nervous system and a commonly known fight-or-flight response. While the response is important for survival, prolonged activation over an extended period of time can have negative effects on health.

After subjecting a group of mice to this chronic stress, researchers tested biological and behavioral hallmarks of the stress response 14 hours and eight days later. At both time points, compared to control mice, the stressed mice showed higher levels of pro-inflammatory proteins in the bloodstream and accumulation of monocytes in the brain, which the scientists had previously linked to anxiety-like behavior – in this case, taking a long time to enter an open space.

“Eight days is a long time for anxiety to persist in a mouse,” Sheridan noted.

By the 24-day point, these markers and behaviors in the stressed mice had returned to baseline levels.

Three groups of mice – the control mice, newly introduced mice to the study and the stress-sensitized mice – were then subjected to acute social defeat: a single two-hour exposure to an aggressive male.

Biological and behavioral markers remained unchanged in the unstressed mice. Within 14 hours after the acute event, the stress-sensitized mice had returned to the chronically stressed state, with higher pro-inflammatory proteins in their blood and a return of anxiety, suggesting monocytes had traveled to the brain to bring on those symptoms.

“That one exposure to an acute stressor produced a similar pattern to what we’d expect to see if they had experienced the chronic stress of repeated social defeat,” Godbout said.

Because a primed immune cell type persisted in the spleen, the researchers removed the spleens of mice after the repeated social defeat-induced sensitization. After that spleen removal, the researchers found that the stress-sensitized mice were no longer sensitive to the acute stressor and the re-establishment of anxiety. The scientists also did not detect immune cell trafficking to the brain or anxiety-like behavior. This finding pointed to the spleen as a source of immune cells responding to the acute stressor.

“Our colleagues who study behavior talk about sensitization,” Sheridan said. “Clearly, the repeatedly stressed mice were sensitized. What we’re adding is that sensitization is associated with a specific cell type that resides in the spleen after the initial sensitization.

“The key is those cells. They originate in the bone marrow but in terms of sensitization, the spleen is a significant organ.”

Sheridan also noted that other scientists are testing blood samples of PTSD patients for biomarkers such as immune cells or pro-inflammatory proteins that might indicate the patients are in a stress-sensitized state.

“This work will validate some of their approaches,” he said.

From here, the researchers plan to compare the profiles of immune cells that travel to the brain versus the spleen during the stress response.

This work was supported by the National Institute of Mental Health and the National Institute on Aging.

Additional co-authors, all from Ohio State, include Eric Wohleb, Daniel McKim, Daniel Shea, Nicole Powell and Andrew Tarr of oral biology (Wohleb and McKim are also affiliated with neuroscience).

Contacts: Jonathan Godbout, (614) 293-3456, Jonathan.Godbout@osumc.edu; or John Sheridan, (614) 293-3571, John.Sheridan@osumc.edu

Written by Emily Caldwell, (614) 292-8310; Caldwell.151@osu.edu

Jonathan Godbout | EurekAlert!
Further information:
http://www.osu.edu

More articles from Life Sciences:

nachricht Building a better battery
29.06.2016 | Texas A&M University

nachricht New way out: Researchers show how stem cells exit bloodstream
29.06.2016 | North Carolina State University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Optical lenses, hardly larger than a human hair

3D printing enables the smalles complex micro-objectives

3D printing revolutionized the manufacturing of complex shapes in the last few years. Using additive depositing of materials, where individual dots or lines...

Im Focus: Flexible OLED applications arrive

R2D2, a joint project to analyze and development high-TRL processes and technologies for manufacture of flexible organic light-emitting diodes (OLEDs) funded by the German Federal Ministry of Education and Research (BMBF) has been successfully completed.

In contrast to point light sources like LEDs made of inorganic semiconductor crystals, organic light-emitting diodes (OLEDs) are light-emitting surfaces. Their...

Im Focus: Unexpected flexibility found in odorant molecules

High resolution rotational spectroscopy reveals an unprecedented number of conformations of an odorant molecule – a new world record!

In a recent publication in the journal Physical Chemistry Chemical Physics, researchers from the Max Planck Institute for the Structure and Dynamics of Matter...

Im Focus: 3-D printing produces cartilage from strands of bioink

Strands of cow cartilage substitute for ink in a 3D bioprinting process that may one day create cartilage patches for worn out joints, according to a team of engineers. "Our goal is to create tissue that can be used to replace large amounts of worn out tissue or design patches," said Ibrahim T. Ozbolat, associate professor of engineering science and mechanics. "Those who have osteoarthritis in their joints suffer a lot. We need a new alternative treatment for this."

Cartilage is a good tissue to target for scale-up bioprinting because it is made up of only one cell type and has no blood vessels within the tissue. It is...

Im Focus: First experimental quantum simulation of particle physics phenomena

Physicists in Innsbruck have realized the first quantum simulation of lattice gauge theories, building a bridge between high-energy theory and atomic physics. In the journal Nature, Rainer Blatt‘s and Peter Zoller’s research teams describe how they simulated the creation of elementary particle pairs out of the vacuum by using a quantum computer.

Elementary particles are the fundamental buildings blocks of matter, and their properties are described by the Standard Model of particle physics. The...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Conference ‘GEO BON’ Wants to Close Knowledge Gaps in Global Biodiversity

28.06.2016 | Event News

ERES 2016: The largest conference in the European real estate industry

09.06.2016 | Event News

Networking 4.0: International Laser Technology Congress AKL’16 Shows New Ways of Cooperations

24.05.2016 | Event News

 
Latest News

Building a better battery

29.06.2016 | Life Sciences

New way out: Researchers show how stem cells exit bloodstream

29.06.2016 | Life Sciences

Crucial peatlands carbon-sink vulnerable to rising sea levels

29.06.2016 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>