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O'Donnell LA , Henkins KM , Kulkarni A , Matullo CM , Balachandran S , Pattisapu AK , Rall GF
Interferon Gamma Induces Protective Non-Canonical Signaling Pathways in Primary Neurons
J Neurochem. 2015 Oct;135(2) :309-22
PMID: 26190522    PMCID: PMC4809142    URL: http://www.ncbi.nlm.nih.gov/pubmed/26190522
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The signal transduction molecule, Stat1, is critical for the expression of type I and II interferon (IFN)-responsive genes in most cells; however, we previously showed that primary hippocampal mouse neurons express low basal Stat1, with delayed and attenuated expression of IFN-responsive genes. Moreover, IFNgamma-dependent resolution of a neurotropic viral challenge in permissive mice is Stat1-independent. Here, we show that exogenous IFNgamma has no deleterious impact on neuronal viability, and staurosporine-induced apoptosis in neurons is significantly blunted by the addition of IFNgamma, suggesting that IFNgamma confers a pro-survival signal in neurons. To identify the pathways induced by IFNgamma in neurons, the activation of alternative signal transducers associated with IFNgamma signaling was assessed. Rapid and pronounced activation of extracellular signal regulated kinase (Erk1/2) was observed in neurons, compared to a modest response in fibroblasts. Moreover, the absence of Stat1 in primary fibroblasts led to enhanced Erk activation following IFNgamma addition, implying that the cell-specific availability of signal transducers can diversify the cellular response following IFN engagement. This article is protected by copyright. All rights reserved.
O'Donnell, Lauren A Henkins, Kristen M Kulkarni, Apurva Matullo, Christine M Balachandran, Siddharth Pattisapu, Anil K Rall, Glenn F J Neurochem. 2015 Oct;135(2):309-22. doi: 10.1111/jnc.13250. Epub 2015 Aug 31.