Abstract book (download .pdf file) - Redox and Inflammation ...

Session 9: Neurodegenerative diseases Poster 14
REGULATION OF INFLAMMATORY PHENOTYPES OF MICROGLIA AND
MICROGLIA-ASTROCYTE COMMUNICATION BY LIVER X RECEPTORS.
Sophie Losciuto, Xavier C. Hever, Tony Heurtaux, Eleonora Morga and Paul
Heuschling
Life Sciences Research Unit, FSTC, University of Luxembourg, 162A, avenue de la
Faïencerie, L-1511 Luxembourg (e-mail: xavier.hever@uni.lu)
Alzheimer’s Disease is a neurodegenerative disorder characterized by the accumulation and
aggregation of Amyloid beta (Ab) peptide. In this pathology, microglia are frequently
activated by a local inflammation, in part caused by the presence of Ab. Pro-inflammatory
compounds secreted by activated microglia attract and activate astrocytes. These astrocytes
also produce pro-inflammatory molecules leading to an inflammatory vicious circle in the
brain accelerating neuronal death. It is known that activated microglia can differentiate
towards a continuous spectrum of phenotypes of which the two extreme states are called M1
for the pro-inflammatory state and M2 for the anti-inflammatory state. The Liver X Receptors
(LXRs) are ligand-activated nuclear receptors known to regulate inflammatory responses by
repressing pro-inflammatory gene expressions in activated microglia.
In this study, Ab was used to induce the M1 pro-inflammatory state of microglia. We first
showed that activated LXR was able to decrease the M1 state of activated microglia but was
not able to induce the M2 anti-inflammatory state. These results suggest that LXR activation
induces in microglia an intermediary state between M1 and M2. Since activated LXR reduces
microglial activation, we analysed whether this effect could have an impact on the cellular
communication between microglia and astrocytes. We showed that LXR activation has no
direct effect on astrocyte activation. In co-culture experiments, preliminary observations
showed that microglia, treated with an LXR agonist, were able to down-regulate astrocytic
activation. Activated LXR appears to be indirectly able to modulate the phenotype of
astrocytes through its action on microglia.
This work emphasizes the role of activated LXR in cellular communication between
microglia and astrocytes. Thus, LXR activation could reduce brain inflammation and may
protect from neuronal death.
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