Submitted on December 4, 2003
Accepted on March 22, 2004
Estrogen Increases Retrograde Labeling of Motoneurons: Evidence of a Non-Genomic Mechanism
Alexander K Murashov1*, Rustem R Islamov1, Roger J McMurray1, Elena S Pak1, and Douglas A Weidner2
1 Physiology, East Carolina University, Greenville, NC, USA
2 Department of Microbiology & Immunology, East Carolina University, Greenville, NC, USA
* To whom correspondence should be addressed. E-mail: murashoval{at}mail.ecu.edu.
Estrogen has a variety of neurotrophic effects mediated via different signaling cascades, including extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3-K) pathways. In this study we investigated effects of estrogen and inhibitors for ERK and PI3-K applied directly onto the cut sciatic nerve on retrograde labeling of lumbar motoneurons. A mix of retrograde tracer (Fluorogold) and 17
-estradiol, in combination with: an antagonist for estrogen receptors ICI 182,780; an inhibitor of ERK1/2 pathway (U0126); an inhibitor of PI3-K (LY 294002); or a protein synthesis inhibitor (cycloheximide) were applied to the proximal stump of the transected sciatic nerve for 24 h. Co-application of Fluorogold with 17-estradiol produced a significant increase in the number of retrograde labeled lumbar motoneurons, compared to Fluorogold alone. Estrogen potentiation of retrograde labeling was inhibited by application of ICI 182,780, U0126, LY 294002 and cycloheximide. Immunohistochemical analysis of the sciatic nerve, 24 h following crush injury, revealed accumulation of phospho-ERK in regenerating nerve fibers. The data suggest a role for estrogen, ERK, PI3-K, and protein synthesis in the uptake and retrograde transport of Fluorogold. We propose that estrogen action in peripheral nerve fibers is mediated via the ERK and PI3-K signaling pathways and is reliant on local protein synthesis.
