Infections in early life, such as those associated with trauma or a viral infection, significantly increase the risk of developing depression in adolescence, according to a Neuron report.
Microglia are the immune cells of the brain and respond to stress. In pathological conditions, activated microglia “manage” brain tissue inflammation, which is closely related to the occurrence and development of depression.
Professor’s team. Zhang Zhi of the College of Life Sciences and Medicine of the University of Science and Technology of China (USTC) and the Chinese Academy of Sciences (CAS), in collaboration with the professor. CAS’ Xu Lin revealed the mechanism by which an inflammatory process in early life leads to depressive symptoms in adolescence.
Clinical studies have shown decreased synaptic density in the anterior cingulate cortex (ACC) and increased inflammation in the brain of depressed patients. The researchers found that inflammation early in life can make microglia prone to random stress events during adolescent development, at which point microglia excessively engulf the dendritic spines of neurons. This impairs the ability of glutamatergic neurons (ACCGlu) in the ACC to resist stress, promoting depression later in life.
To study the stress response of ACC microglia during the development of mice from infancy to adolescence (45 days postnatal), the scientists modeled inflammation by intraperitoneal administration of lipopolysaccharide (LPS) in a critical time window of brain development (14 days postnatal).
After 6 h of LPS injection, many markers of ACC microglia activation in mice were significantly increased and returned to previous levels after 24 h. Later in development, a series of unpredictable stressful events (such as weaning, confinement, noise, and combat) can lead to reactivation of ACC microglia in LPS-injected mice that are more susceptible to this activation than normal mice.
Moreover, the increase in ACCGlu activity before stress occurred helped the mice survive the stress. However, ACC microglia in inflammatory mice are often activated early in life by persistent stress during adolescence and over-acting on the fissured spines of ACCGlu neurons, thus reducing ACCGlu activity. As a result, the body’s ability to deal with stress declined, which contributed to depression in teenage mice. (PAP)
Author: Pawe Wernicki
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