The role of the aryl hydrocarbon receptor in glial cells during demyelination
Author(s): ,
S.N. Schmid
Neuropathology, University Medical Center Göttingen, Göttingen, Germany
W. Brück
Neuropathology, University Medical Center Göttingen, Göttingen, Germany
N. Kramann
Neuropathology, University Medical Center Göttingen, Göttingen, Germany
ECTRIMS Online Library. Schmid S. Oct 12, 2018; 228136; P1758
Susanne, Nicole Schmid
Susanne, Nicole Schmid
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Abstract: P1758

Type: Poster Sessions

Abstract Category: N/A

Mice with reduced astrocytic NF-κB activation are protected from cuprizone-induced demyelination. The Aryl hydrocarbon receptor (AhR) is a potent immunoregulator that restricts NF-κB activation via direct interaction with its p65 subunit. Increased expression of AhR reduces inflammation within the central nervous system. Therefore, we investigated AhR depletion in glial cells during cuprizone-induced demyelination and its function in regulating astrocytic NF-κB activity.
We selectively blocked AhR signaling in GFAP- and Aldh1l1-positive astrocytes and CX3CR1-positive microglia by using the Cre/lox system. GFAP serves as a reliable marker labelling nearly all reactive astrocytes that are responding to CNS injury. However, since it only targets a limited number of astrocytes, we also used the marker aldehyde dehydrogenase 1 family member L1 (Aldh1l1) to analyse the functional impact of AhR inactivation in the overall astrocyte population. Demyelination, inflammation, axonal damage and glial pathology were evaluated after cuprizone challenge. Using primary cells we tested for effects on NF-κB activation in astrocytes and microglia.
Astrocytic AhR-depletion does not prevent mice from cuprizone-induced demyelination, microglial activation, axonal transections and oligodendroglial apoptoses in vivo. However, using a reporter-based in vitro assay, NF-κB activity is significantly reduced in AhR-depleted primary astrocytes after stimulation as compared to wild type astrocytes in vitro.
These findings suggest that AhR-depletion in primary astrocytes is feasible to significantly reduce astrocytic NF-κB activity in vitro. This mechanism may be compensated in vivo. Therefore, the AhR signaling pathway must be investigated in more detail to evaluate whether it is a useful tool for preventive interventions and a valuable target of therapeutic approaches.
Susanne Schmid: nothing to disclose
Wolfgang Brück: nothing to disclose
Nadine Kramann: nothing to disclose

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