RT Journal Article
SR Electronic
T1 Reduction of Potassium Currents and Phosphatidylinositol 3-Kinase-Dependent Akt Phosphorylation by Tumor Necrosis Factor-α Rescues Axotomized Retinal Ganglion Cells from Retrograde Cell Death <em>In Vivo</em>
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2058
OP 2066
DO 10.1523/JNEUROSCI.21-06-02058.2001
VO 21
IS 6
A1 Ricarda Diem
A1 Roman Meyer
A1 Jochen H. Weishaupt
A1 Mathias Bähr
YR 2001
UL http://www.jneurosci.org/content/21/6/2058.abstract
AB Tumor-necrosis-factor-α (TNF-α) prevented secondary death of retinal ganglion cells (RGCs) after axotomy of the optic nervein vivo. This RGC rescue was confirmed in vitro in a mixed retinal culture model. In accordance with our previous findings, TNF-α decreased outward potassium currents in RGCs. Antagonism of the TNF-α-induced decrease in outward potassium currents with the potassium channel opener minoxidilsulfate (as verified by electrophysiology) abolished neuroprotection. Western blot analysis revealed an upregulation of phospho-Akt as a consequence of TNF-α-induced potassium current reduction. Inhibition of the phosphatidylinositol 3-kinase–Akt pathway with wortmannin decreased TNF-α-promoted RGC survival. These data point to a functionally relevant cytokine-dependent neuroprotective signaling cascade in adult CNS neurons.