Joint research by Kobe University and Kyoto University has revealed that innate immune system inflammation in the brain is important for inducing depression due to stress.
Psychological stress received from society and the environment brings about various mental and physical changes.Moderate stress induces the defense response of the living body, but excessive stress induces mental changes such as depression and becomes a risk factor for depression.
So far, inflammatory cytokines have increased in the blood of depressed patients, microglia, which are the cells responsible for inflammation, have been activated in the brains of depressed patients, and the incidence of depression in patients with chronic inflammatory diseases has increased. It has been reported that it is high, and it has been suggested that depression is associated with inflammation.However, there were many unclear points in the causal relationship.
This research group aimed to clarify the mechanism by which repetitive stress induces depression using the repetitive social frustration stress model, which is an animal model of depression.As a result, repetitive social frustration stress activates microglia in the medial prefrontal cortex via the innate immune receptors TLR2 and TLR4 in the brain, and the activated microglia are inflammatory such as IL-1α and TNFα. It was found that it releases cytokines and induces responsive attenuation and atrophy of neurons in the medial prefrontal cortex, as well as depressive behavior (social repellent behavior).
This result suggests that the functional changes of nerve cells in the medial prefrontal cortex due to inflammation in the brain are important for the pathophysiology of depression, leading to the development of new antidepressants targeting innate immune molecules. It presents the possibility.
Furthermore, in the future, by investigating the mechanism of action of inflammatory cytokines derived from microglia, it will be possible to approach the functional changes of the neural circuits responsible for the pathophysiology of depression.
Paper information:[Neuron] The Innate Immune Receptors TLR2 / 4 Mediate Repeated Social Defeat Stress-Induced Social Avoidance through Prefrontal Microglial Activation
