Coexpression of mRNAs for NGF, BDNF, and NT-3 in the cardiovascular system of the pre- and postnatal rat

The expression of NGF, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) mRNAs was examined in whole rat embryos and in the heart and great vessels of postnatal and adult rats, using in situ hybridization of cRNA probes. The patterns of expression were correlated with innervation patterns as revealed by immunostaining for neural cell adhesion molecule (NCAM) and with the HNK-1 antibody, which demonstrates derivatives of the neural crest. The patterns of neurotrophin mRNA localization were different from those of mRNAs for the low-molecular-weight NGF receptor. Hybridization indicating the presence of mRNAs for all three neurotrophins is particularly prominent within the tunica media of the aorta, pulmonary, and other major elastic arteries of the thorax and abdomen and is first observed on embryonic day 13 (E13) when innervation is being established and rises to maximum by E15. In the fetus, there is little or no detectable expression in the CNS or PNS. NT-3 expression in the vessels is relatively constant and high from embryonic to adult stages, while levels of BDNF increase and those of NGF decrease over the same time course. During the fetal period, hybridization in the heart is absent. In the postnatal period, additional label becomes detectable in the coronary arteries but not in the walls of the atria or ventricles, other than at the base of the aorta and pulmonary trunk. The pattern of expression of the three neurotrophins suggests that all three may be expressed by the same muscle cells of the elastic arteries and therefore may act on the same postganglionic or sensory neurons innervating the great vessels and coronary arteries. Neurotrophin mRNA expression by muscle cells in the major elastic arteries occurs only after nerve fibers have arrived at the vessels and correlates with the derivation of these distributing arteries from cardiac neural crest cells. Changes in expression of neurotrophin mRNAs over the course of development, and their continued expression in the adult, suggest that members of the NGF neurotrophin family are likely to play different roles at different stages of development.