Endocrine influence on neuroinflammation: the use of reporter systems

Most of the ageing-associated pathologies are coupled with a strong inflammatory component that accelerates the progress of the physiopathological functional decline related to ageing. The currently available pharmacological tools for the control of neuroinflammation present several side effects that restrict their application, particularly in chronic disorders. The discovery of the potential anti-inflammatory action exerted by endogenous oestrogens, as well as the finding that activation of oestrogen receptor α results in a significant decrease of inflammation at the cellular level and in models of inflammatory diseases, prompted us to embark in a series of studies aimed at the generation of reporter systems, allowing us to (i) understand the anti-inflammatory action of oestrogens at molecular level; (ii) evaluate the extent to which the action of this steroid hormone was relevant in models of pathologies characterised by a strong inflammatory component; and (iii) investigate the efficacy of novel, synthetic oestrogens endowed with anti-inflammatory activity. Accordingly, we conceived the NFκB-luc2 reporter mouse, a model characterised by dual reporter genes for fluorescence and bioluminescence imaging under the control of a synthetic DNA able to bind the transcription factor nuclear factor kappa B, the master regulator of the expression of most of the cytokines responsible for the initial phase of acute inflammation. Here, we summarise the philosophy that has driven our research in the past years, as well as some of the results obtained so far.