Neuron-glia interactions in the CNS : implication of CXCR3 signaling in excitotoxicity-induced neurodegeneration

Abstract

In this thesis we provide evidence that microglia have a profound neuroprotective role in a paradigm known as glutamate-induced neurodegeneration (excitotoxicity) and that local expression of chemotactic cytokines (chemokines) considerably affects the degree of neuronal cell death in this paradigm. More specifically, we demonstrate that chemokines CXCL10 and CCL21 directly affect neuronal survival under excitotoxic conditions, most likely through modulation of microglia activation. Moreover, we provide evidence that the effects of these two chemokines in this paradigm are mediated through the same chemokine receptor, namely CXCR3. Finally, we demonstrate that CXCL10 and CCL21 induce calcium transients and proliferation in astrocytes in vitro, suggesting also a role for these chemokines in the activation of astrocytes.