Nerve Growth Factor Control of Neuronal Expression of Angiogenetic and Vasoactive Factors

• Published in: Proceedings of the National Academy of Sciences - PNAS 2001-03, Vol.98 (7), p.4160-4165
• Main Authors: Calzà, Laura, Giardino, Luciana, Giuliani, Alessandro, Aloe, Luigi, Levi-Montalcini, Rita
• Format: Article
• Language: English
• Subjects: Adrenergic Agents - pharmacology; Angiogenesis; Angiogenesis Inducing Agents - metabolism; Animals; Animals, Newborn; Biological Sciences; Cell growth; Connective tissues; Endothelial cells; Endothelial Growth Factors - metabolism; Histology; Immunohistochemistry; Lymphokines - metabolism; Mice; Neovascularization, Physiologic - drug effects; Nerve Growth Factor - pharmacology; Nerve tissue; Nerves; Neurology; Neurons; Neurons - drug effects; Neurons - metabolism; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type I; Oxidopamine - pharmacology; Rats; Superior cervical ganglion; Superior Cervical Ganglion - drug effects; Superior Cervical Ganglion - metabolism; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Vasodilation - drug effects
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.051626998

In postnatal tissues, angiogenesis occurs in nontumoral conditions on appropriate stimuli. In the nervous tissue, hypoxia, neural graft, increased neural function, and synaptic activity are associated with neoangiogenesis. We have investigated the occurrence of neoangiogenesis in the superior cervical ganglia (scg) of newborn rats treated for 8-21 days with 6-hydroxy-dopamine (6-OHDA), nerve growth factor (NGF), or 6-OHDA + NGF. The two latter treatments induced a significant increase in scg size. However, the increase after combined treatment far exceeded that of NGF alone. Similarly, histological and histochemical analysis revealed neuronal hypertrophy and endothelial cell hyperplasia associated with stromal hypertrophy (as described by laminin immunostaining) and increased vascular bed (as revealed by platelet/endothelial cell adhesion molecule-1 immunostaining) in 6-OHDA + NGF-treated pups. NGF, either alone or associated with 6-OHDA, also induced a significant up-regulation of NADPH diaphorase, neuronal nitric oxide synthase, and vascular endothelial growth factor expression in scg neurons. The present investigation suggests that the increase of scg size induced by NGF and 6-OHDA + NGF is associated with neoangiogenesis, and that the induction of vasoactive and angiogenic factors in neurons represents a further and previously undisclosed effect of NGF.