Activació/inhibició del factor de transcripció NF-kB en neurones i cèl.lules glials mitjançant l'ús de vectors no-vírics

Recent studies suggest that glial cell activation is tightly related to the activation of specific transcription factors such as NF-kB. It is known that NF-kB activation in glial cells regulates the transcription of several genes involved in the immune and inflammatory responses. However, activation of NF-kB in neuronal cells has been suggested to be beneficial for neuronal survival. The aim of this basic science project is to interact with the activation of the transcription factor NF-kB in glial cells, with the purpose of reducing the negative consequences that this activation may have on experimentally induced neurodegenerative processes and lesion outcome. Parallely, by promoting the activation of NF-kB in neuronal cells we will try to favour the neuroprotective actions of this transcription factor. The experimental procedure we propose is based in the use of well characterised experimental lesions (cortical excitotoxic lesions and retrograde thalamic degeneration induced cortical aspiration lesions) and the use of non-viral vectors to transfer specific gene sequences under adequate promoters for the specific gene expression in glial and neuronal cells. Finally, by using the same gene transfer technology, we will try to complete with the activation of NF-kB in glial cells after injury by tranfering genes encoding for trophic factors, antioxidant proteins and anti-immflamatory cytokines, endogenous modulators of the glial response that reduce neuronal damage. One part of the study will be based on the use of histological techniques, mainly immunohistochemistry, and the other part will be based on the use of antibody-linked membranes (AntibodyArrays) and western blotting from brain homogenates