Affective Immunology: The Crosstalk Between Microglia and Astrocytes Plays Key Role?

Abstract

Emerging evidence demonstrates the critical role of the immune response in the mechanisms relating to mood disorders, such as major depression (MDD) and bipolar disorder (BD). This has cast a spotlight on a specialized branch committed to the research of dynamics of the fine interaction between emotion (or affection) and immune response, which has been termed as "affective immunology." Inflammatory cytokines and gut microbiota are actively involved in affective immunology. Furthermore, abnormalities of the astrocytes and microglia have been observed in mood disorders from both postmortem and molecular imaging studies; however, the underlying mechanisms remain elusive. Notably, the crosstalk between astrocyte and microglia acts as a mutual and pivotal intermediary factor modulating the immune response posed by inflammatory cytokines and gut microbiota. In this study, we propose the "altered astrocyte-microglia crosstalk (AAMC)" hypothesis which suggests that the astrocyte-microglia crosstalk regulates emotional alteration through mediating immune response, and thus, contributing to the development of mood disorders.

Keywords: astrocyte-microglia crosstalk; bipolar disorder; depression; mood disorders; neuroinflammation.

Figure 1

Schematic illustration of three cornerstones of affective immunology.

Figure 2

Schematic illustration of the fine interaction between astrocytes and microglia during neuroinflammation. Reactive microglia activate and determine the phenotypes of astrocytes, ranging from neurotoxic to neuroprotective. The reactive neurotoxic astrocytes promote the capacity of microglial activation, motility, and phagocytosis, while weakening the blood-brain barrier (BBB) and prune synapses. Increased BBB permeability facilitates the recruitment of immune cells and diffusion of inflammatory cytokines, amplifying neuroinflammatory response. The reactive neuroprotective astrocyte can lead to microglial inactivation, synaptogenesis, and scar formation.