Models of neuronal plasticity and repair in the enteric nervous system: a review.

In the Fifties we developed an experimental model of neuronal plasticity in adulthood, involving the intestinal myenteric plexus. Causing an incomplete stenosis of the gut, the thickness of the wall and the diameter of the lumen underwent a massive increase on the oral side of the obstruction. The myenteric neurons innervating such hypertrophic and hyperplastic smooth muscle became hypertrophic and increased their number per ganglion, in absence of mitoses. Therefore we hypothesized the existence of a reserve pool of morphologically undifferentiated elements within the plexus, undergoing differentiation under conditions of functional hyperactivity. Some recent experiments suggest once again the existence in adulthood of a reserve pool of potential neurons. In fact, we put in evidence a subpopulation of NADPH-diaphorase positive myenteric neurons, very small in size orally to the stenosis and even smaller in the control gut. Following experimental ablation of the myenteric plexus in an intestinal segment and induction of hypertrophy in its smooth muscle layers, we found a two-five-fold increase in neuronal density along mesenteric nerves. This increase is probably due to the recruitment of cells, not readily identifiable as neurons, along mesenteric nerves in an attempt to reinnervate the damaged ileum. Moreover, it is demonstrated that hypertrophic smooth muscle cells may induce neuronal differentiation of transplanted PC12 cells. Finally, we explain the decreased total number of myenteric neurons in advanced age with the exhaustion of this reserve pool: in fact, NADPH-diaphorase positive small neurons in the myenteric plexus of old rats could not be found.