Previous Article |
Table of Contents
| Next Article 
BIOLOGICAL SCIENCES / MEDICAL SCIENCES
Activation of Trk neurotrophin receptors by glucocorticoids provides a neuroprotective effect
*Molecular Neurobiology Program, Departments of Cell Biology, Physiology, and Neuroscience and Psychiatry, Kimmel Center for Biology and Medicine of the Skirball Institute of Biomolecular Medicine, and Department of Microbiology, New York University School of Medicine, New York, NY 10016
Edited by Bruce S. McEwen, The Rockefeller University, New York, NY, and approved January 30, 2008 (received for review September 24, 2007)
Glucocorticoids (GCs) display both protective and destructive effects in the nervous system. In excess, GCs produce neuronal damage after stress or brain injury; however, the neuroprotective effects of adrenal steroids also have been reported. The mechanisms that account for the positive actions are not well understood. Here we report that GCs can selectively activate Trk receptor tyrosine kinases after in vivo administration in the brain and in cultures of hippocampal and cortical neurons. Trk receptors are normally activated by neurotrophins, such as NGF and brain-derived neurotrophic factor, but the activation of Trk receptors by GCs does not depend on increased production of neurotrophins. Other tyrosine kinase receptors, such as EGF and FGF receptors, were not activated by GCs. The ability of GCs to increase Trk receptor activity resulted in the neuroprotection of neurons deprived of trophic support and could be modulated by steroid-converting enzymes. Pharmacological and shRNA experiments indicate that Trk receptor activation by GCs depends on a genomic action of the GC receptor. The ability of GCs to promote Trk receptor activity represents a molecular mechanism that integrates the actions of GCs and neurotrophins.
signaling | trans-activation | hippocampus | tyrosine phosphorylation
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0709102105/DC1.
To whom correspondence may be addressed. E-mail: jeannete{at}saturn.med.nyu.edu or chao{at}saturn.med.nyu.edu
© 2008 by The National Academy of Sciences of the USA
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg What's this?
