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Involvement of GPR17 in Neuronal Fibre Outgrowth

Characterization of new pharmacological targets is a promising approach in research of
neurorepair mechanisms. The G protein-coupled receptor 17 (GPR17) has recently been proposed as
an interesting pharmacological target, e.g., in neuroregenerative processes. Using the well-established
ex vivo model of organotypic slice co-cultures of the mesocortical dopaminergic system (prefrontal
cortex (PFC) and substantia nigra/ventral tegmental area (SN/VTA) complex), the influence of
GPR17 ligands on neurite outgrowth from SN/VTA to the PFC was investigated. The growthpromoting
effects of Montelukast (MTK; GPR17- and cysteinyl-leukotriene receptor antagonist),
the glial cell line-derived neurotrophic factor (GDNF) and of two potent, selective GPR17 agonists
(PSB-16484 and PSB-16282) were characterized. Treatment with MTK resulted in a significant increase
in mean neurite density, comparable with the effects of GDNF. The combination of MTK and GPR17
agonist PSB-16484 significantly inhibited neuronal growth. qPCR studies revealed an MTK-induced
elevated mRNA-expression of genes relevant for neuronal growth. Immunofluorescence labelling
showed a marked expression of GPR17 on NG2-positive glia. Western blot and RT-qPCR analysis of
untreated cultures suggest a time-dependent, injury-induced stimulation of GPR17. In conclusion,
MTK was identified as a stimulator of neurite fibre outgrowth, mediating its effects through GPR17,
highlighting GPR17 as an interesting therapeutic target in neuronal regeneration.

Identiferoai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89187
Date22 January 2024
CreatorsBraune, Max, Scherf, Nico, Heine, Claudia, Sygnecka, Katja, Pillaiyar, Thanigaimalai, Parravicini, Chiara, Heimrich, Bernd, Abbracchio, Maria P., Müller, Christa E., Franke, Heike
PublisherMDPI
Source SetsHochschulschriftenserver (HSSS) der SLUB Dresden
LanguageEnglish
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text
Rightsinfo:eu-repo/semantics/openAccess
Relation11683

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