Kurzfassung

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, an altered 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 LPS, contrasting it with the response of microglia under control conditions. Our analysis included calcium imaging, migration assays, phagocytosis assays, immunocytochemistry and the evaluation of surface marker expression (CD40). For our study, we mainly employed cultures of BV-2 cells, a murine microglia cell line, and performed preliminary experiments with a human microglia cell line (C20) and primary human microglia-like cells, differentiated from peripheral blood mononuclear cells.

We observed that a pro-inflammatory environment accentuated the response of microglia to NE, leading to an increase in the intracellular calcium signaling and cell migration. Contrary, 5-HT did not lead to Ca2+ evoked responses nor to altered cell migration in both resting and pro-inflammatory conditions. Moreover, chronic treatment of microglia with NE lead to a desensitization of microglia, whereas chronic 5-HT treatment also increased the responsiveness of microglia to acute NE application, but not to 5-HT. On the other hand, monoamines significantly decreased the expression of the microglia activation marker CD40, which is upregulated under pro-inflammatory conditions. Yet, despite the findings described above, monoamine treatment did not lead to altered phagocytic capacity of BV-2 microglia.

These results suggest that the inflammatory environment influences the complex and subtle balance between levels of monoamines and microglia response. 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.