Figure 1.

P2X7R activation is necessary and sufficient for enteric neuron death. (a) GFAP (green) and P2X7 (magenta) immunoreactivity in the mouse colon myenteric plexus. (scale bar = 20 μm). Bottom right panel shows an enlarged view of a GFAP–ir glial cell embracing a P2X7–ir enteric neuron (boxed area in overlay). Scale bar = 5 μm. (b) Mean packing density of myenteric neurons is significantly reduced in DNBS (2,4-dinitrobenzene sulfonic acid; n = 4 animals), DSS (dextran sodium sulfate; n = 8), oxazolone (n = 6 animals), and interleukin 10 knockout (I/10^−/−; n = 4) models of experimental colitis. ANOVA with **P < 0.001 and ***P < 0.0001 versus respective control. (c) Representative myenteric ganglia from control (Saline), inflamed (Saline-DNBS), or mice pre-treated with the P2X7R inhibitor oxidized ATP before being inflamed (oATP-DNBS) labeled with the pan-neuronal marker HuC/D (scale bar = 50 μm). (d) Mean packing density of HuC/D–ir neurons in the myenteric plexus (**P < 0.001 versus saline, ANOVA, n = 5 animals saline, 4 DNBS saline treated, 3 EtOH, 3 oATP and 4 DNBS oATP treated). Macroscopic damage and weight loss for treatment groups shown in (e) and (f), respectively. (g) Mean packing density of HuC/D–ir neurons after in situ activation of P2X7Rs with BzATP alone or with various inhibitors (*P<0.05, **P<0.001, ***P<0.0001 versus buffer, ANOVA, n = 10 animals buffer, 10 BzATP, 3 zVAD, 3 IL-1ra, 3 ¹⁰Panx, and 3 scPeptide).