Rungtip SoiampornkulLiqi TongWipawan ThangniponRobert BalazsCarl W. CotmanMahidol UniversityUniversity of California, Irvine2018-07-122018-07-122008-01-10Brain Research. Vol.1188, No.1 (2008), 189-197000689932-s2.0-37349000213https://repository.li.mahidol.ac.th/handle/20.500.14594/18989It was previously observed that IL-1β interferes with BDNF-induced TrkB-mediated signal transduction and protection of cortical neurons from apoptosis evoked by deprivation from trophic support [Tong L., Balazs R., Soiampornkul R., Thangnipon W., Cotman C.W., 2007. Interleukin-1beta impairs brain derived neurotrophic factor-induced signal transduction. Neurobiol. Aging]. Here we investigated whether the effect of the cytokine on neurotrophin signaling is more general. The influence of IL-1β on NT-3 signaling was therefore studied under conditions when NT-3 primarily activated the TrkC receptor. The cytokine reduced NT-3-induced activation of MAPK/ERK and Akt, but did not interfere with Trk receptor autophosphorylation. IL-1β reduced tyrosine phosphorylation of the docking proteins, IRS-1 and Shc, which convey receptor activation to the downstream protein kinase cascades. These are the steps that are also inhibited by IL-1β in BDNF-induced signal transduction. The functional consequences of the effect of IL-1β on NT-3 signaling were severe, as NT-3 protection of the trophic support-deprived cortical neurons was abrogated. In view of the role in the maintenance and plasticity of neurons of ERK, Akt and CREB, which are activated by neurotrophins, elevated IL-1β levels in the brain in Alzheimer's disease and other neurodegenerative diseases might contribute to the decline in cognitive functions before the pathological signs of the disease develop. © 2007 Elsevier B.V. All rights reserved.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyMedicineNeuroscienceArticleSCOPUS10.1016/j.brainres.2007.10.051