About My Health Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

Stress Susceptibility may be Reversed by Boosting Natural Resilience

by Kathy Jones on April 20, 2014 at 9:42 PM
Font : A-A+

 Stress Susceptibility may be Reversed by Boosting Natural Resilience

Out-of-balance electrical activity inside neurons of the brain's reward circuit is responsible for vulnerability to depression-like behaviors in mice, say scientists, who have experimentally reversed this vulnerbility.

Instead of suppressing it, researchers funded by the National Institutes of Health boosted runaway neuronal activity even further, eventually triggering a compensatory self-stabilizing response. Once electrical balance was restored, previously susceptible animals were no longer prone to becoming withdrawn, anxious, and listless following socially stressful experiences.

Advertisement

"To our surprise, neurons in this circuit harbor their own self-tuning, homeostatic mechanism of natural resilience," explained Ming-Hu Han, Ph.D., of the Icahn School of Medicine at Mount Sinai, New York City, a grantee of the NIH's National Institute of Mental Health (NIMH) and leader of the research team.

Han and colleagues report on their discovery April 18, 2014 in the journal Science.

"As we get to the bottom of a mystery that has perplexed the field for more than a decade, the story takes an unexpected twist that may hold clues to future antidepressants that would act through this counterintuitive resilience mechanism." said NIMH Director Thomas R. Insel, M.D.
Advertisement

Prior to the new study, the researchers had turned resilience to social stress on and off by using pulses of light to manipulate reward circuit neuronal firing rates in genetically engineered mice - optogenetics. But they didn't know how resilience worked at the cellular level.

To find out, they focused on electrical events in reward circuit neurons of mice exposed to a social stressor. Some mice that experience repeated encounters with a dominant animal emerge behaviorally unscathed, while others develop depression-like behaviors.

Neurons that secrete the chemical messenger dopamine from a reward circuit hub called the ventral tegmental area (VTA) become abnormally hyperactive in the susceptible mice. This excess activation is known to be triggered by an excitatory electrical current that drives cell firing. Han and colleagues were surprised to discover that this excitatory current was even higher in the stress-resilient mice even though they were spared the runaway dopamine activity and depression-related behaviors. Yet neurons of these resilient mice also showed a simultaneous increase in inhibitory potassium channel currents.

This prompted the researchers to hypothesize that in resilient animals the runaway excitatory current triggers the boost in the inhibitory current in a self-balancing mechanism, resulting in normal mood-related behaviors. By this logic, perhaps the susceptible mice just needed a boost in excitatory currents to activate their compensatory currents.

To test this, Han's team repeatedly infused the VTA of susceptible mice, over five days, with a drug known to increase the excitatory current. As hypothesized, the animals showed a profound reversal in behaviors and antidepressant-like effects - they socialized more and their characteristic rodent sweet tooth came back.

At the cellular level, this was accompanied by a marked increase in both the excitatory and inhibitory currents, resulting in normalized neuronal activity. The drug the mice received, lamotrigine, is clinically used as a mood stabilizer to treat the depressed phase of bipolar disorder - and the researchers may have discovered its mechanism of action.

Han and colleagues also achieved similar results using chronic optogenetic stimulation to drive up the neuronal activity. However, they discovered that the homeostatic mechanism seems to work specifically in the reward circuit - projections of the VTA to the nucleus accumbens - and not in VTA projections to the prefrontal cortex.

The abnormally high excitatory current that develops in response to social stress -if driven high enough for a sustained period - triggers its own compensatory adaptation, the inhibitory currents that corrects out-of-balance electrical activity and produces resilience. So at least in the brain's reward circuit, exaggerating an abnormality, for a time, proved to be the curative secret , say the researchers.

"Homeostatic mechanisms finely regulate other critical components of physiology required for survival - blood glucose and oxygen, body temperature, blood pressure," explained Lois Winsky, Ph.D., chief of the NIMH Molecular, Cellular, and Genomic Neuroscience Research Branch, which funded the study. "Similar mechanisms appear to also maintain excitatory balance in brain cells. This study shows how they may regulate circuits underlying behavior."



Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
News Category
What's New on Medindia
Breast Cancer Awareness Month 2021 - It's time to RISE
First-Ever Successful Pig-To-Human Kidney Transplantation
World Osteoporosis Day 2021 -
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
Palpitations And Arrhythmias Stress Relief Through Alternative Medicine Stress and the Gender Divide Andropause / Male Menopause Heart Attack- Lifestyle Risks Is Your Man Moody? Tired All The Time Women More Prone to Road Rage Quiz on Weight Loss Stress 

Recommended Reading
Stress and the Gender Divide
Stress has become entwined in the current lifestyle of a young working couple and has resulted in .....
Post Traumatic Stress Disorder
Post Traumatic Stress Disorder (PTSD), is a mental condition triggered by a traumatic event. PTSD .....
Exercise Stress Test
A stress test is used to test for heart disease. Exercise stress test is also called exercise ......
Andropause / Male Menopause
Andropause or male menopause causing low libido in a man is due to decreasing level of male hormones...
Heart Attack- Lifestyle risks
Heart attack is the death of the heart muscle due to loss of blood supply. Simple guidelines to avoi...
Is Your Man Moody?
Women get confused by the behavior of men in their lives. It is time they realize that men too have ...
Palpitations And Arrhythmias
Palpitations are unpleasant sensation of one’s own heartbeat....
Tired All The Time
Tired All The Time (TATT) syndrome is not only about feeling of tired, however there are a host of o...
Women More Prone to Road Rage
If you find your self getting mad and cursing under your breath while driving, you are a victim of r...

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2021

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use