| The protective properties of adenosine via adenosine A1 receptors in neurons subjected to excitotoxicity are well established. Our group has previously shown that Interleukin (IL)-6 up regulated the expression and function of neuronal adenosine A1 receptors (Biber et al., 2001), which was accompanied by an enhanced neuroprotection (Biber et al., 2007). The intracellular signaling events that are involved in IL-6-dependent induction of adenosine A1 receptor expression are not yet understood. Neither is known whether other IL-6 type cytokines exert their neuroprotective effects by an induction of adenosine A1 receptors. Research and future plans In my PhD project, neuroprotective properties of other IL-6-type cytokine family members such as Leukemia Inhibitory Factor (LIF), Oncostatin M (OSM), and Ciliary Neurotrophic Factor (CNTF), will be investigated and their effects on expression and function of adenosine A1 receptors will be studied. Furthermore, the dependency of cytokine mediated neuroprotection on adenosine A1 receptors will be investigated in the receptor knock-out mice. The signaling pathway involved in the cytokine induced-adenosine A1 receptor mediated neuroprotection will be investigated by specific inhibition of the two major signaling pathways (STAT and ERK/MAPK). Methods used in this project are primary cell culture, organotypic brain slice cultures, assays for cytotoxicity and molecular biology. |
