Early Exposure to Inflammation Could Induce Depression in Adolescence

A team at the Chinese Academy of Sciences has revealed the mechanisms by which early-life inflammation induces depression symptoms during adolescence. Their work was published in Neuron. 

In their study, the researchers found that early-life inflammation would lead to the susceptibility of microglial in the ACC to random stress events during adolescent development, and microglia then engulfed dendritic spines of neurons. This weakened the ability of ACC glutamatergic neuronal (ACCGlu) to fight stress, thus inducing adolescent depression.

To explore the responding and activating model of ACC microglia to stress during mouse development from childhood to adolescence (45 days after birth), researchers established an inflammatory model by intraperitoneal administration of lipopolysaccharide (LPS) during the critical time window of mouse brain development (14 days after birth). Six hours after LPS injection, multiple activation indexes of ACC microglia in mice significantly increased and recovered after 24 hours. Interestingly, during the later development, a series of unpredictable life stress events (such as weaning, caging, noise, and fighting) could lead to the reactivation of ACC microglia in LPS mice, being more susceptible than normal mice.

Moreover, before stress, the sharp increase of ACCGlu activity helped mice resist the attack of stress and protect themselves. However, ACC microglia of mice with early-life inflammation were frequently activated by persistent stress in adolescence, and over engulfed the ACCGlu dendritic spines via CX3CR1 signals mediate, consequently reducing the activity of ACCGlu. As a result the body's ability to cope with stress was impaired, which promoted depression in adolescent mice.