Abundant production of brain-derived neurotrophic factor by adult visceralepithelia - Implications for paracrine and target-derived neurotrophic functions

Brain-derived neurotrophic factor (BDNF) plays a crucial role for the survi val of visceral sensory neurons during development. However, the physiologi cal sources and the function of BDNF in the adult viscera are poorly descri bed. We have investigated the cellular sources and the potential role of BD NF in adult murine viscera. We found markedly different amounts of BDNF pro tein in different organs. Surprisingly, BDNF levels in the urinary bladder, lung, and colon were higher than those found in the brain or skin. In Situ hybridization experiments revealed that BDNF mRNA was made by visceral epi thelial cells, several types of smooth muscle, and neurons of the myenteric plexus. Epithelia that expressed BDNF lacked both the high- and low-affini ty receptors for BDNF, trkB and p75(NTR). In contrast, both receptors were present on neurons of the peripheral nervous system. Studies with BDNF-/-mi ce demonstrated that epithelial and smooth muscle cells developed normally in the absence of BDNF. These data provide evidence that visceral epithelia are a major source, but not a target, of BDNF in the adult viscera. The ab undance of BDNF protein in certain internal organs suggests that this neuro trophin may regulate the function of adult visceral sensory and motor neuro ns.