Issues

The picture represents well known brain-to-body cholinergic anti-inflammatory pathway: acetylcholine (ACh, red sphere) released from the vagus nerve (representative cholinergic neuron depicted in red) stimulates production of norepinephrine (green sphere) in the splenic nerve that triggers release of ACh from a splenic T cell and subsequent activation of anti-inflammatory secondary signaling mechanisms (including NF-κB, JAK-STAT pathways, etc.) in splenic macrophages via stimulation of the α7 nicotinic acetylcholine receptor (α7 nAChR, red receptor) resulting in lower production of pro-inflammatory cytokines (TNFα, IL-1β, IL-6, IL-8). This circuit is activated by pro-inflammatory cytokines at the sensory fibers of the vagus nerve, and the related neuroinflammation process involves interaction of cholinergic neurons with microglia, astrocytes, oligodendrocytes, and dendritic cells in the brain.