Expression of retinoid X receptor β is induced in astrocytes during corpus callosum demyelination.
The experimental activation of retinoid receptors reduces pathological symptoms in animal models of multiple sclerosis. In order to assess the involvement of endogenous retinoid signaling during the process of demyelination we investigated retinoic acid synthesizing enzymes and nuclear receptors using the mouse model of cuprizone toxicity. The initiation of myelin degradation in the corpus callosum was accompanied with a local increase of retinaldehyde dehydrogenase (RALDH) immunoreactivity. On the level of receptors we observed a striking increase in protein expression of the retinoid X receptor (RXR)-β in the affected corpus callosum. The RXRβ immunoreactivity appeared exclusively in astrocytes, where it reached a maximum at five weeks of treatment, following the RALDH response. In the cerebral cortex and basal ganglia of affected mice RXRβ was also observed in neurons. Among nuclear receptor antigens RARα showed a cuprizone associated increase in the corpus callosum. Quantitative RT-PCR revealed strong basal expression of RXRβ and a significant, over 20-fold upregulation of the peroxisome proliferator-activated receptor-γ during demyelination. The results indicate that compensatory mechanisms during central demyelination may engage nuclear receptor dimers with an RXRβ partner.
Institut für Biologie II, RWTH Aachen, Germany.
René
R
König
Milena
M
Stillfried
Philipp
P
Aperdannier
Tim
T
Clarner
Cordian
C
Beyer
Markus
M
Kipp
Jörg
J
Mey
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003337:Corpus Callosum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003471:Cuprizone / Q000633:toxicity; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D049230:Retinoid X Receptor beta / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D049230:Retinoid X Receptor beta; D003471:Cuprizone