Myenteric Neurons Do Not Replicate in Small Intestine Under Normal Physiological Conditions in Adult Mouse

Enteric Neurons Get Our Undivided Attention

“…How do we reconcile these disparate images of the ENS? The former scenario of stability is easier to fathom, but more importantly is consistent with multiple published studies (all cited by Virtanen et al 2 ) that show minimal neurogenesis in healthy adult intestine. It is unclear what factors contributed to Kulkarni et al's 1 result as compared with the other studies, but aside from potential methodologic issues, biologic variation and environmental factors could play a role.…”

“…Many questions remain regarding enteric neurogenesis in the adult gut: what are the signals that activate it, which are the progenitor cells, what types of neurons can be generated, and how can this be leveraged for regenerative therapies to treat neurointestinal diseases? We are grateful to Virtanen et al, 2 Kulkarni et al, 1 and others who have contributed to this discussion and are leading us on a journey toward understanding this important aspect of gastrointestinal physiology.…”

“…In this issue of Cellular and Molecular Gastroenterology and Hepatology , Virtanen et al 2 set out to replicate those results using the same methods as the original study. Adult mice were given the thymidine analogue, IdU, in their drinking water for 7 days at the same concentration and duration as Kulkarni et al.…”

Detection of mitotic neuroblasts provides additional evidence of steady state neurogenesis in the adult enteric nervous system

“…Compared to the arduous and complex protocols required for detection of thymidine analogues such as BrdU in adult enteric neurons 7 , our current report provides a simpler method to show the presence of neurogenesis in the adult ENS, and provides a tool that can be used to test alterations in the rate of neurogenesis in response to disease or intervention. In a recent report and subsequent correspondence, Virtanen et al 16,17 were unable to detect any thymidine analogues in myenteric neurons and suggested that proliferation of glial cells and turnover of neurons in the adult small intestinal ENS are rare events. Although we and others use multiple lines of evidence to show the presence of apoptosis in the adult healthy myenteric neurons of the murine gut [4][5][6][7][18][19][20] , Virtanen et al opined that at least for some of these studies, the observations of a significant rate of apoptosis in myenteric neurons may be due to sampling biases, and that based on their lack of BrdU detection, there is little DNA replication in adult enteric neurons in a healthy gut 16,19 .…”

Enteric nervous system regeneration and functional cure of experimental digestive Chagas disease with trypanocidal chemotherapy

“…There are several potential neurogenic mechanisms that could underly this replenishment. It has been proposed that enteric neurons are regularly replaced from a population of neural stem cells as part of gut homeostasis (44), however, the majority of studies indicate that enteric neurogenesis is absent, or extremely limited in the steady-state adult gut (45)(46)(47)(48)(49)(50). Regeneration of the ENS involves neurogenesis from enteric glial cell pre-cursors after chemical injury using benzalkonium chloride (BAC) or Dextran Sulfate Sodium (DSS) (46,47,49,50) and from extrinsic Schwann cell pre-cursors in mouse models of Hirschprung's disease (51,52).…”