Regulation of NGF and NT-3 protein expression in peripheral targets by sympathetic input.

Abstract:

:Nerve growth factor (NGF) and neurotrophin-3 (NT-3) are target-derived proteins that regulate innervating sympathetic neurons. Here, we used western blot analysis to investigate changes in NGF and NT-3 protein in several peripheral tissues following loss of sympathetic input. Following removal of the superior cervical ganglion (SCG), large molecular weight (MW) NGF species, including proNGF-A, were increased in distal intracranial SCG targets, such as pineal gland and extracerebral blood vessels (bv). Mature NGF was a minor species in these tissues and unchanged following sympathectomy. Large MW NGF species also were increased when sympathectomy was followed by in vivo NGF administration. Mature NT-3, which was abundant in controls, was significantly decreased in these targets following sympathetic denervation. The decrease in mature NT-3 was enhanced following NGF administration. The trigeminal ganglion, which provides sensory input to these targets, showed increased NGF, but decreased NT-3, in these treatments, demonstrating that decreased NT-3 at the targets did not result from enhanced NT-3 uptake. Unlike pineal gland and extracerebral bv, the external carotid artery, an extracranial proximal SCG target, showed no change in NGF following denervation, and mature NT-3 was significantly increased. Following NGF administration, NT-3 was significantly decreased. We provide evidence for sympathetic regulation of NGF and NT-3 in peripheral targets and that elevated NGF can depress NT-3. The differential response in distal and proximal adult targets is consistent with the idea that neurons innervating proximal and distal targets may serve different roles in regulating neurotrophin protein. In addition, we conclude that previous ELISA results showing increased NGF protein following sympathetic denervation may have resulted from increases in large MW species, rather than an increase in mature NGF.

journal_name

Brain Res

journal_title

Brain research

authors

Randolph CL,Bierl MA,Isaacson LG

doi

10.1016/j.brainres.2007.01.099

subject

Has Abstract

pub_date

2007-05-04 00:00:00

pages

59-69

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(07)00257-0

journal_volume

1144

pub_type

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