Localization of α7 nicotinic acetylcholine receptor mRNA and protein within the cholinergic anti-inflammatory pathway

• α7 Nicotinic receptor mRNA is highly expressed in celiac/mesenteric ganglionic complex.
• α7 Nicotinic receptor mRNA is expressed in the spleen at low levels.
• α7 Nicotinic receptors are present on noradrenergic neurons in the ganglionic complex.
• α7 Nicotinic receptors are localized to noradrenergic nerve fibers in the spleen.
• The results further implicate neuronal α7 receptors in anti-inflammatory circuitry.

Electrical stimulation of the vagus nerve attenuates tumor necrosis factor (TNF) synthesis by macrophages and reduces the systemic inflammatory response. Current evidence suggests that the α7 nicotinic acetylcholine receptor present in the celiac/superior mesenteric ganglia is a key component in vagus nerve signaling to the spleen; however, there is currently no direct anatomical evidence that the α7 receptor is present in the murine celiac/superior mesenteric ganglia. Our study addresses this deficiency by providing anatomical evidence that the α7 receptor is expressed within the celiac/superior mesenteric ganglia and splenic nerve fibers using immunohistochemistry and quantitative polymerase chain reaction (qPCR). α7 receptor mRNA is highly expressed in the celiac/superior mesenteric ganglia and at low levels in the spleen compared to the brain. Double-labeling for α7 and tyrosine hydroxylase shows that α7 receptor protein is present on noradrenergic neurons within the ganglia and prejunctionally on noradrenergic nerve fibers within the spleen. The α7 receptor in the ganglia provides a possible location for the action of α7-selective agonists, while prejunctional α7 receptor expressed on splenic nerves may induce an increase in norepinephrine release in a positive feedback system enhanced by lymphocyte-derived acetylcholine.