Figure 7. Degenerative changes to myenteric plexus and delayed intestinal transit in FoxO3^−/− mice.

Immunostaining of LMMP from FoxO3^−/− and WT FVB mice from 3 age groups (3 months, 12 months, and 20 months) with pan-neuronal marker HuC/D (red) and pSTAT3 (green) revealed increased numbers of Hu⁺ neurons expressing pSTAT3 (arrows) in FoxO3^−/− compared to WT mice in the mid and old age groups (A). Expressed as percent of neurons (pSTAT3⁺Hu⁺/total Hu⁺), this difference was statistically significant for the mid and old age groups. An increased number of Hu⁺ neurons (red) co-expressing cleaved caspase-3 (Asp175, green, arrow) was also found in FoxO3^−/− compared to WT mice and was statistically significant in all age groups (B). A statistically significant decline in neuronal density (Hu⁺ cells/ganglia area (100 μm²)) in was observed in FoxO3^−/− compared to WT mice was observed in the 3 month and 12 month age groups but not the 20 month group (C). Prolonged intestinal transit times were found in FoxO3^−/− mice compared to WT (performed on a separate cohort of male mice between the age of 14–17 months). Representative images are from 12-month age group. *p<.05, **p<.01, and ***p<.001 by multiple t-test. Scale bars, 50 μm.