Evidence for the presence and release of BDNF in the neuronal and non-neuronal structures of the internal anal sphincter

Background Data on the neuromodulatory effects of brain-derived neurotrophic factor (BDNF) in the gastrointestinal tract were recently reported, but there are still no data on the presence, distribution, and release of BDNF in the gastrointestinal tract, including the internal anal sphincter (IAS). Methods We examined the presence and distribution of BDNF and its receptor TrkB in the different IAS structures (neuronal and non-neuronal) via immunohistochemical and immunocytochemical analyses. We also monitored the release of BDNF in an IAS muscle bath (consisting of smooth muscle cells [SMCs], myenteric plexus, and submucosal plexus) before and after different agonists, and electrical field stimulation in the absence and presence of neurotoxin tetrodotoxin. Key Results BDNF/TrkB was found to be present in all layers of the IAS, especially the smooth muscle, mucosa, myenteric plexus, and submucosal plexus. Detailed analyses revealed a significant colocalization between BDNF and TrkB in different structures, especially in the smooth muscle, the SMCs, and both plexuses. Data further showed higher levels of BDNF in the cytosol and that of TrkB toward the periphery of the SMCs. Conclusions & Inferences These studies showed that BDNF/TrkB was present not only in the enteric nervous system (ENS), but also in the SMCs. For the neuromodulatory effects, BDNF is released locally from the ENS ((myenteric (10.01 +/- 0.23 pg/ml) and submucosal plexus (9.05 +/- 0.51 pg/ml)) and the SMCs (18.63 +/- 1.63 pg/ml). Collectively, these findings have pathophysiological and therapeutic implications regarding the role of BDNF/TrkB in the IAS-associated rectoanal motility disorders.