Infusion of C20 ceramide induces depressive‐like behavior, increases microglia but not astrocyte expression

Abstract

Depression is a disease affecting the population worldwide. Depressed patients have shown alteration in the hippocampus suggesting this region can be an important region to study the impact of the development of depressive‐like behavior. Literature has demonstrated depressed patients present an increased levels of long‐chain ceramides. Ceramide is a sphingolipid component of the cellular membrane and play an important role in its structural integrity. To better understand depression mechanisms it is important to assess the glial cells mechanisms, since these cells play an essential role in inflammation, which is increased in depressed patients. Literature has reported interaction between astrocytes and microglia, still their detailed mechanism, their individual response to ceramide signaling, and contribution to depressive‐like behavior development are not clearly understood. Some research has demonstrated that microglia are activated in the presence of C20 and C16 ceramide. Otherwise, data have shown that reactive astrocytes interact with C16 ceramide but not with C24 ceramides. Because of this, we hypothesize that the infusion of long‐chain ceramides (C20) in the ventral hippocampus will increase the development of depressive‐like behavior, will cause an increase in the level of microglia expression but not astrocyte expression. We performed seven infusions of long‐chain ceramides into the ventral hippocampus followed by behavior analysis to measure the development of depressive‐like behavior and tissue collection to analyze inflammatory profile. Results show that rats infused with long‐chain ceramides present development of short‐term anhedonia‐like behavior twenty‐four hours after infusions but no depressive‐like behavior was assessed five days after the last infusion of ceramides. Also, infusion of ceramides induce an increase in microglia expression but no significant differences were assessed in astrocyte expression. These results suggest that C20 ceramide activates the microglia inflammatory pathway but not astrocyte mediated inflammation. There might be different mechanisms inducing inflammation in microglia and astrocytes. This preliminary data can also suggest that microglia mediated inflammation can contribute more to depressive‐like behavior than astrocytes. These results bring speculative significance, but more comprehensive studies can show a higher understanding of ceramide signaling in inflammation and a better understanding of the contribution of microglia and astrocytes to the development of depressive‐like behavior.