An integrative study of neuroinflammation in the brain

Abstract

Neuroinflammation is a common trait shared for most of neurodegenerative diseases, and as more evidence are gathered, it is been hypothesized as not only a deviation but also the trigger of them. The main players in an inflammatory response in the brain are glial cells, mainly microglia. Microglia and astrocytes are able to respond to external and internal stimuli developing a wide-range of reactive phenotypes. Although glial activation is a physiological beneficial response, an exacerbated or maintained glial activation may have neurotoxic effects. A series of inhibitory mechanisms, mediated by soluble molecules and cell-cell contact, maintain microglial activation under control in physiological conditions. It is suggested that neurons play a relevant role in the control of glial activation, but cross-talk between the different cells of the CNS may also be involved. In this project neuroinflammation has been addressed from three different perspectives in three parallel projects. Firstly, the study of the potential therapeutic potential against neurodegenerative disease of the PPAR-ϒ agonist MIN-102 was tested in both mixed glial cultures, using nitrite oxide production as an indicative of the inflammatory state. Secondly, the study of the control of neuroinflammation by neuron and microglia cross-talk focusing on the CD200-CD200R1 axis, using CD200 KO mice. Lastly, the study of the immune response of astrocytes was address under the exposure to parkinsonian toxins MPP+ and rotenone treatment of mouse astrocytes-enriched primary cultures. This way, MIN-102 didn‟t lessen the nitrite production result of the immune response, but other parameters are now being studying. Frozen embryos of CD200KO mouse has been generated, allowing a future CD200KO strain mouse generation. Finally, we successfully developed a primary astrocyte-enriched culture protocol, that is being used to characterise astrocyte response to neurotoxicants.