Brain-derived neurotrophic factor amplifies neurotransmitter responses and promotes synaptic communication in the enteric nervous system.
BACKGROUND
Besides its role in neuronal growth and differentiation, brain-derived neurotrophic factor (BDNF) has been implicated in the control of peristalsis where it serves to enhance gastrointestinal motility.


OBJECTIVE
To unravel the cellular mechanisms governing BDNF's effect on motility.


METHODS
Studies were performed in primary myenteric neuron cultures and whole-mount preparations derived from guinea pig ileum. Expression of BDNF and its tropomyosin-related kinase B (TrkB) receptor was assessed by immunohistochemistry. Intracellular Ca(2+) concentration ([Ca(2+)](i)) changes in myenteric neurons were monitored using Fluo-4, and neurotransmitter release kinetics at enteric synapses were evaluated with FM1-43 imaging.


RESULTS
Immunohistochemistry revealed the presence of BDNF and TrkB in mucosa, submucosal plexus and myenteric ganglia. Primary cultures also expressed BDNF and TrkB and were used to study the physiological effects of BDNF. None of the neurons studied displayed a [Ca(2+)](i) change when challenged with BDNF. However, BDNF exposure caused an enhancement of Ca(2+) transients induced by serotonin and substance P, which was reversed by the Trk receptor blocker K-252a (0.1 microM). BDNF exposure also resulted in an amplification of spontaneous network activity which was reflected in an increased number of synaptic vesicle clusters. Furthermore, BDNF treatment facilitated FM1-43-labelled vesicle destaining in enteric terminals during field stimulation.


CONCLUSIONS
The findings demonstrate that BDNF is able to enhance rather than directly activate enteric nervous system signalling. Therefore, the promotion of motility by BDNF seems to result from its potent modulating role on enteric neuronal activity and synaptic communication.
Boesmans
W
W
Center for Gastroenterological Research, KULeuven, Herestraat 49, Lab 701, B-3000 Leuven, Belgium.
Gomes
P
P
Janssens
J
J
Tack
J
J
Vanden Berghe
P
P
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D017615:Enteric Nervous System / Q000502:physiology*; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D012701:Serotonin; D013373:Substance P; D020813:Receptor, trkB; D002118:Calcium