Increased NGF proforms in aged sympathetic neurons and their targets.
Target-derived neurotrophins such as nerve growth factor (NGF) and neurotrophin-3 (NT-3) regulate sympathetic neuron survival. Here, NGF and NT-3 protein and transcript were examined in sympathetic neurons and targets in order to determine their role in age-related neuronal atrophy. One obvious alteration was a dramatic increase (up to 50-fold) in NGF protein forms, corresponding to proNGF-B, in the superior cervical ganglion (SCG) and targets where sympathetic innervation shows atrophy. In the iris, where sympathetic innervation is protected into old age, proNGF-B was decreased. Alterations in NGF transcript paralleled changes in NGF protein, albeit to a lesser degree. Though significantly increased in aged SCG, NT-3 protein, found primarily as the 'mature' form, showed only minor changes in most tissues, though NT-3 mRNA generally was decreased. In contrast, both NT-3 transcript and NT-3 precursors were increased in iris. The dramatic increases in proNGF, together with minimal changes in NT-3, suggest that alterations in NGF regulation may contribute to the loss of sympathetic innervation observed in many aged peripheral targets.
Bierl
Michael A
MA
Center for Neuroscience, Department of Zoology, Miami University, Oxford, OH 45056, USA.
Isaacson
Lori G
LG
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D005260:Female; D020932:Nerve Growth Factor / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013564:Sympathetic Nervous System / Q000502:physiology*; D014018:Tissue Distribution; D015533:Transcriptional Activation / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
D020933:Neurotrophin 3; D020033:Protein Isoforms; D020932:Nerve Growth Factor