Local control of inflammation neuronal damage by Peroxisome-profilator-activated receptory (PPARy) in EAE

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During the last funding period, we were able to show that ablation of the nuciear receptor PPARy in myeloid cells enhances CNS inflammation during the effector phase of EAE, which was associated with an increased activation status of PPARy-ablated cells within the CNS. We now plan to further explore the protective effects of PPARy on inflammation-associated neuronal damage. We propose the existence of a PPARy-mediated neuroprotective cross-talk between local immune cells and neurons within the CNS. First, we will determine the protective influence of PPARy in microglia and invading monocytes on inflammation-induced neuronal damage in brain slice cultures. We will assess whether PPARy results in altematively activated macrophages and microglial cells exhibiting anti-inflammatory and neuroprotective properties. Moreover, we plan to identify the functional relevance of endogenous PPARy ligands produced locally within the CNS for the generation of a neuroprotective milieu and alleviation of inflammation-induced neurotoxicity in vivo. Together, our study will help to identify the therapeutic potential of PPARy in myeloid cells for targeting CNS autoimmunity by enhancing neuroprotective interactions between immune cells and neuronal cells.