Nav: Home

Neural inflammation plays critical role in stress-induced depression

July 19, 2018

A group of Japanese researchers has discovered that neural inflammation caused by our innate immune system plays an unexpectedly important role in stress-induced depression. This insight could potentially lead to the development of new antidepressants targeting innate immune molecules. The findings were published on July 20 (Japan Standard Time) in the online edition of Neuron.

The joint study was led by Professor Tomoyuki Furuyashiki and Assistant Professor Shiho Kitaoka (Kobe University Graduate School of Medicine) in collaboration with Project Professor Shuh Narumiya (Kyoto University Graduate School of Medicine).

Previous research had already hinted at the link between inflammation and depression: increased levels of inflammation-related cytokines in the blood of patients suffering from depression, activation of microglia (inflammation-related cells in the brain) in depressive patients, and a high percentage of depression outbreaks in patients suffering from chronic inflammatory disease. However, the exact relationship between depression and inflammation still contains many unknowns.

Psychological stress caused by social and environmental factors can trigger a variety of changes in both mind and body. Moderate levels of stress will provoke a defensive response, while extreme stress can lower our cognitive functions, cause depression and elevated anxiety, and is a risk factor for mental illnesses. The research team focused on repeated social defeat stress (a type of environmental stress) with the aim of clarifying the mechanism that causes an emotional response to repeated stress.

First, they looked at changes of gene expression in the brain caused by repeated social defeat stress and found that repeated stress increased a putative ligand for the innate immune receptors TLR2 and TLR4 (TLR2/4) in the brain. Their next step was to investigate the role of TLR2/4 in repeated stress using a mouse with the TLR2/4 genes deleted. They found that TLR2/4-deficient mice did not show social avoidance or extreme anxiety when exposed to repeated stress. Repeated stress usually triggers microglial activation in specific areas of the brain such as the medial prefrontal cortex, causing impaired response and atrophy of neurons, but these responses were not present in the TLR2/4-deficient mice.

The research team then developed a method to selectively block the expression of TLR2/4 in the microglia of specific areas of the brain. By blocking the expression of TLR2/4 in the microglia of the medial prefrontal cortex, they managed to suppress depressive behavior in response to repeated social defeat stress. They found that repeated stress induced the expression of inflammation-related cytokines IL-1α and TNFα in the microglia of the medial prefrontal cortex via TLR2/4. The depressive behavior was suppressed by treating the medial prefrontal cortex with neutralizing antibodies for the inflammation-related cytokines.

These results show that repeated social defeat stress activates microglia in the medial prefrontal cortex via the innate immune receptors TLR2/4. This triggers the expression of inflammation-related cytokines IL-1α and TNFα, leading to the atrophy and impaired response of neurons in the medial prefrontal cortex, and causing depressive behavior.

Professor Furuyashiki says: "These findings demonstrate the importance of neural inflammation caused by the innate immune system for stress-induced depression. This could lead to the development of new antidepressant medication targeting innate immune molecules".
-end-


Kobe University

Related Depression Articles:

Tackling depression by changing the way you think
A thought is a thought. It does not reflect reality.
How depression can muddle thinking
Depression is associated with sadness, fatigue and a lack of motivation.
Neuroimaging categorizes 4 depression subtypes
Patients with depression can be categorized into four unique subtypes defined by distinct patterns of abnormal connectivity in the brain, according to new research from Weill Cornell Medicine.
Studies suggest inflammatory cytokines are associated with depression and psychosis, and that anti-cytokine treatment can reduce depression symptoms
Studies presented at this year's International Early Psychosis Association meeting in Milan, Italy, (Oct.
Is depression in parents, grandparents linked to grandchildren's depression?
Having both parents and grandparents with major depressive disorder was associated with higher risk of MDD for grandchildren, which could help identify those who may benefit from early intervention, according to a study published online by JAMA Psychiatry.
Postpartum depression least severe form of depression in mothers
Postpartum depression -- a household term since actress Brooke Shields went public in 2005 about her struggle with it -- is indeed serious.
Tropical Depression 1E dissipates
Tropical Depression 1E or TD1E didn't get far from the time it was born to the time it weakened to a remnant low pressure area along the southwestern coast of Mexico.
Diagnosing depression before it starts
MIT researchers have found that brain scans may identify children who are vulnerable to depression, before symptoms appear.
Men actually recommend getting help for depression
Participants in a national survey read a scenario describing someone who had depressed symptoms.
Depression too often reduced to a checklist of symptoms
How can you tell if someone is depressed? The Diagnostic and Statistical Manual of Mental Disorders (DSM) -- the 'bible' of psychiatry -- diagnoses depression when patients tick off a certain number of symptoms on the DSM checklist.

Related Depression Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Changing The World
What does it take to change the world for the better? This hour, TED speakers explore ideas on activism—what motivates it, why it matters, and how each of us can make a difference. Guests include civil rights activist Ruby Sales, labor leader and civil rights activist Dolores Huerta, author Jeremy Heimans, "craftivist" Sarah Corbett, and designer and futurist Angela Oguntala.
Now Playing: Science for the People

#520 A Closer Look at Objectivism
This week we broach the topic of Objectivism. We'll be speaking with Keith Lockitch, senior fellow at the Ayn Rand Institute, about the philosophy of Objectivism as it's taught through Ayn Rand's writings. Then we'll speak with Denise Cummins, cognitive scientist, author and fellow at the Association for Psychological Science, about the impact of Objectivist ideology on society. Related links: This is what happens when you take Ayn Rand seriously Another Critic Who Doesn’t Care What Rand Thought or Why She Thought It, Only That She’s Wrong Quote is from "A Companion to Ayn Rand"