Early cellular signaling responses to axonal injury
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BioMed Central
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Early cellular signaling responses to axonal injury Thomas J Lukas*1,3, Ai Ling Wang1,2, Ming Yuan1,2 and Arthur H Neufeld1,2 Address: 1Forsythe Laboratory for the Investigation of the Aging Retina, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA, 2Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA and 3Department of Molecular Pharmacology & Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA Email: Thomas J Lukas* - [email protected]; Ai Ling Wang - [email protected]; Ming Yuan - [email protected]; Arthur H Neufeld - [email protected] * Corresponding author
Published: 13 March 2009 Cell Communication and Signaling 2009, 7:5
doi:10.1186/1478-811X-7-5
Received: 17 October 2008 Accepted: 13 March 2009
This article is available from: http://www.biosignaling.com/content/7/1/5 © 2009 Lukas et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: We have used optic nerve injury as a model to study early signaling events in neuronal tissue following axonal injury. Optic nerve injury results in the selective death of retinal ganglion cells (RGCs). The time course of cell death takes place over a period of days with the earliest detection of RGC death at about 48 hr post injury. We hypothesized that in the period immediately following axonal injury, there are changes in the soma that signal surrounding glia and neurons and that start programmed cell death. In the current study, we investigated early changes in cellular signaling and gene expression that occur within the first 6 hrs post optic nerve injury. Results: We found evidence of cell to cell signaling within 30 min of axonal injury. We detected differences in phosphoproteins and gene expression within the 6 hrs time period. Activation of TNFα and glutamate receptors, two pathways that can initiate cell death, begins in RGCs within 6 hrs following axonal injury. Differential gene expression at 6 hrs post injury included genes involved in cytokine, neurotrophic factor signaling (Socs3) and apoptosis (Bax). Conclusion: We interpret our studies to indicate that both neurons and glia in the retina have been signaled within 30 min after optic nerve injury. The signals are probably initiated by the RGC soma. In addition, signals activating cellular death pathways occur within 6 hrs of injury, which likely lead to RGC degeneration.
Introduction Axonal damage of long projecting neurons leads to retrograde degeneration and loss of the soma of the neuron by programmed cell death over a period of several days. However, little is known about the timing of events in the soma of the neuron immediately following damag
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