Rate of neuronal turnover in the healthy adult murine myenteric ganglia varies with ganglia size

Abstract

AbstractMajor gastrointestinal and systemic functions are regulated by the Enteric Nervous System (ENS), whose cells are organized in interconnected clusters or ganglia to form plexuses in the gut wall. Previously, we showed that neuronal turnover, driven by overall equal rates of neurogenesis and neuronal loss, is an important homeostatic mechanism that maintains the larger myenteric plexus of the healthy adult ENS. While this process maintains neuronal numbers, whether it occurs at the same rate across the two sexes, in different regions and within ganglia that contain a diversity of neuronal numbers remains unknown. Here, by using antibodies against the DNA replication marker phospho-Histone H3 and against the pan-neuronal marker Hu to detect new-born neurons, we observe that while the proportions of new-born myenteric neurons are conserved irrespective of the region or sex in the healthy small intestine, they are inversely correlated with ganglia size. In contrast, by using antibodies against the apoptosis marker Cleaved Caspase 3 and Hu, we found that proportions of apoptotic neurons were directly correlated with ganglia size. Our observations on the unequal rate of neuronal turnover across ganglia, where smaller ganglia are more neurogenic and larger ganglia are more apoptotic, suggests that the myenteric ganglia are plastic in nature. These results provide further insight into the dynamic nature of the adult ENS.