G-Protein-Coupled Receptor Gpr17 Expression in Two Multiple Sclerosis
Received: 22 January 2018 /Accepted: 22 May 2018
Springer Science+Business Media, LLC, part of Springer Nature 2018
In multiple sclerosis patients, demyelination is prominent in both the white and gray matter. Chronic clinical deficits are
known to result from acute or chronic injury to the myelin sheath and inadequate remyelination. The underlying molecular
mechanisms of remyelination and its failure remain currently unclear. Recent studies have recognized G protein-coupled
receptor 17 (GPR17) as an important regulator of oligodendrocyte development and remyelination. So far, the relevance of
GPR17formyelinrepairwasmainlytestedinremyelinatingwhite matter lesions. The relevance of GPR17 for gray matter
remyelination as well as remyelination of chronic white matter lesions was not addressed so far. Here, we provide a
detailed characterization of GPR17 expression during experimental de- and remyelination. Experimental lesions with
robust and limited endogenous remyelination capacity were established by either acute or chronic cuprizone-induced
demyelination. Furthermore, remyelinating lesions were induced by the focal injection of lysophosphatidylcholine
(LPC) into the corpus callosum. GPR17 expression was analyzed by complementary techniques including immunohisto-
chemistry, in situ hybridization, and real-time PCR. In control animals, GPR17
cells were evenly distributed in the corpus
callosum and cortex and displayed a highly ramified morphology. Virtually all GPR17
cells also expressed the
oligodendrocyte-specific transcription factor OLIG2. After acute cuprizone-induced demyelination, robust endogenous
remyelination was evident in the white matter corpus callosum but not in the gray matter cortex. Endogenous callosal
remyelination was paralleled by a robust induction of GPR17 expression which was absent in the gray matter cortex.
Higher numbers of GPR17
cells were as well observed after LPC-induced focal white matter demyelination. In contrast,
densities of GPR17
cells were comparable to control animals after chronic cuprizone-induced demyelination indicating
quiescence of this cell population. Our findings demonstrate that GPR17 expression induction correlates with acute
demyelination and sufficient endogenous remyelination. This strengthens the view that manipulation of this receptor might
be a therapeutic opportunity to support endogenous remyelination.
1. Cortical remyelination is delayed in the cuprizone model.
2. GPR17 expression is induced in the white but not gray matter.
3. GPR17 expression is induced in acute, but not chronic lesions.
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s12035-018-1146-1) contains supplementary
material, which is available to authorized users.
* Markus Kipp
Institute of Neuroanatomy and JARA-BRAIN, Faculty of Medicine,
RWTH Aachen University, 52074 Aachen, Germany
Department of Anatomy II, Ludwig-Maximilians-University of
Munich, 80336 Munich, Germany
Neurosciences TA Biology, UCB BioPharma, Braine L’Alleud,