BDNF SUPPORTS MAMMALIAN CHEMOAFFERENT NEURONS IN-VITRO AND FOLLOWING PERIPHERAL TARGET REMOVAL IN-VIVO

Chemoreceptor neurons innervating the rat carotid body were used as a model system to define target regulation of visceral sensory developme nt in fetal and newborn animals. In vitro, chemoafferents were selecti vely supported by co-culture with the carotid body or by treatment wit h trkB ligands [brain-derived neurotrophic factor (BDNF) and neurotrop hin-4], whereas nerve growth factor and neurotrophin 3 had no effect. In vivo, chemoafferent neurons died following carotid body removal at birth, indicating a predominant role of peripheral, rather than centra l, targets in mediating survival at this stage. However, in the absenc e of target tissues, a large proportion of carotid body afferents coul d be rescued by implants containing BDNF. Moreover, BDNF mRNA was dete cted in the newborn carotid body by reverse transcriptase polymerase c hain reaction. These data provide the first demonstration that BDNF ca n substitute for peripheral target support of sensory neuron survival in vivo and indicate that trkB ligands may be particularly important f or development of visceral afferents involved in cardiorespiratory con trol. (C) 1994 Academic Press, Inc.