Monoaminergic modulation of microglia in physiological and inflammatory conditions

The activity of microglia, the resident immune cells of the central nervous system (CNS), is controlled by various neurotransmitters and modulators. For instance, monoamines such as serotonin (5-HT) and norepinephrine (NE), have been reported to modulate the physiological functions of microglia. However, altered concentrations of monoamines have been observed in pathologies of the CNS, such as Alzheimer's disease or major depressive disorder. Remarkably, changes in monoamine levels happen in synchrony with altered microglial functions during CNS diseases. Thus, a reduced immune modulation through monoamines may affect the course of pathologies.Hence, we investigated the modulation of monoamines on microglia in a pro-inflammatory state induced by the application of Lipopolysaccharide (LPS), contrasting it with the response of microglia under control conditions. Our analysis included calcium imaging, migration assays, phagocytosis assays, and the evaluation of surface marker expression (CD40) employing cultures of BV-2 cells, a murine microglia cell line.We observed that a pro-inflammatory environment accentuated the response of microglia to monoamines, leading to an increase in the intracellular calcium signaling and cell migration. On the other hand, monoamines significantly decreased the expression of the microglia activation marker CD40, which is upregulated under pro-inflammatory conditions.These results suggest that the inflammatory environment influences the complex and subtle balance between levels of monoamines and microglia responsiveness. Hence, there is a need for further investigation into the synergistic impact on neuronal function, connectivity, and plasticity resulting from altered monoaminergic signaling affecting both microglia and neurons simultaneously.