Adult enteric nervous system in health is maintained by a dynamic balance between neuronal apoptosis and neurogenesis

Abstract

According to current dogma, there is little or no ongoing neurogenesis in the fully developed adult enteric nervous system. This lack of neurogenesis leaves unanswered the question of how enteric neuronal populations are maintained in adult guts, given previous reports of ongoing neuronal death. Here, we confirm that despite ongoing neuronal cell loss because of apoptosis in the myenteric ganglia of the adult small intestine, total myenteric neuronal numbers remain constant. This observed neuronal homeostasis is maintained by new neurons formed in vivo from dividing precursor cells that are located within myenteric ganglia and express both Nestin and p75NTR, but not the pan-glial marker Sox10. Mutation of the phosphatase and tensin homolog gene in this pool of adult precursors leads to an increase in enteric neuronal number, resulting in ganglioneuromatosis, modeling the corresponding disorder in humans. Taken together, our results show significant turnover and neurogenesis of adult enteric neurons and provide a paradigm for understanding the enteric nervous system in health and disease.

The role of the gut microbiota in development, function and disorders of the central nervous system and the enteric nervous system

“…It was long assumed that neurogenesis does not occur in the ENS in adult mice during normal conditions, although it could be induced by injury . However, more recent studies suggest that the ENS in adult mice is capable of maturation and plasticity, and that neurogenesis of enteric neurones can occur . Studies suggest that 5‐HT stimulates enteric neurogenesis, and modulation of 5‐HT levels during ENS development may therefore have long‐lasting effects on the ENS function .…”

Intraganglionic macrophages: a new population of cells in the enteric ganglia

“…) and MHCII (Kulkarni et al. ) in mice. The immunophenotype of the IMs, however, supports the idea that these cells may represent microglia.…”

“…Similar ramified cells expressing major histocompatibility complex (MHC) class II (Kulkarni et al. ), and macrophage markers, including CD163, CD11b, CSF1R, Iba1, and F4/80 (Mikkelsen, ; Mikkelsen et al. ; Orandle et al.…”

“…MMs were also shown to phagocytose apoptotic enteric neurons (Kulkarni et al. ), a role that resembles the ‘scavenger’ activity of CNS microglia. Genomic hierarchical clustering, based on a 39‐gene macrophage signature, revealed that intestinal macrophages show the strongest relationship to CNS microglia (Gautiar et al.…”

Intestinal Neuronal Dysplasia Type B: An Updated Review of a Problematic Diagnosis

“…50 Most of the basic research has focused on myenteric ganglia and murine models. According to a recently published study, enteric neurons undergo postnatal homeostatic apoptosis and replacement by stem cells, 51 although this finding is controversial. 52 Stimuli shown to drive postnatal enteric neurogenesis include tissue injury, 53 whereas neurogenesis in response to obstruction/ distension alone has not been documented.…”