Fig. 11.

Hypothetical model for microglia as source of LTs in the brain. Key elements of the LTs synthesis pathway are FLAP and 5-Lox, which are co-expressed in some microglia cells (green). Additionally, 5-Lox staining was observed in neurons (blue). It is known that 5-Lox and FLAP protein need to form an intracellular complex to start the synthesis pathway resulting in the production of LTs (left panel). With the herein shown microglia ablation experiment (+PLX5622), we could confirm microglia cells as potential source for LTs. In microglia ablated brains (right panel) FLAP and 5-Lox expression as well as CysLTR1 was highly decreased. Additionally, our data supports the idea of a putative microglia neuron interaction, as 5-Lox immunoreactivity was reduced in neurons of microglia ablated WT brains. LTs thereby possibly affect microglia in an autocrine manner via the CysLTR1, and neurons via GPR17. We hypothesize a putative feedback loop between neurons and microglia involving LTs signaling in the context of neuroinflammation. Image was created with BioRender.com