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Article

Involvement of GPR17 in Neuronal Fibre Outgrowth

1
Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, University of Leipzig, Härtelstr. 16-18, 04107 Leipzig, Germany
2
Methods and Development Group Neural Data Analysis and Statistical Computing, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1A, 04103 Leipzig, Germany
3
Department of Pharmaceutical & Medicinal Chemistry, Pharmaceutical Institute, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany
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Department of Pharmaceutical Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy
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Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Center for Basics in NeuroModulation, Faculty of Medicine, University of Freiburg, Albertstr. 23, 79104 Freiburg, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Dmitry Aminin and Peter Illes
Int. J. Mol. Sci. 2021, 22(21), 11683; https://doi.org/10.3390/ijms222111683
Received: 4 October 2021 / Revised: 24 October 2021 / Accepted: 24 October 2021 / Published: 28 October 2021
(This article belongs to the Special Issue Purinergic Signaling in Neuroinflammation)
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 growth-promoting 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. View Full-Text
Keywords: G protein-coupled receptor 17 (GPR17); neurite outgrowth; montelukast; NG2; ex vivo organotypic brain slice co-culture; neurodegeneration and neuroregeneration G protein-coupled receptor 17 (GPR17); neurite outgrowth; montelukast; NG2; ex vivo organotypic brain slice co-culture; neurodegeneration and neuroregeneration
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MDPI and ACS Style

Braune, M.; Scherf, N.; Heine, C.; Sygnecka, K.; Pillaiyar, T.; Parravicini, C.; Heimrich, B.; Abbracchio, M.P.; Müller, C.E.; Franke, H. Involvement of GPR17 in Neuronal Fibre Outgrowth. Int. J. Mol. Sci. 2021, 22, 11683. https://doi.org/10.3390/ijms222111683

AMA Style

Braune M, Scherf N, Heine C, Sygnecka K, Pillaiyar T, Parravicini C, Heimrich B, Abbracchio MP, Müller CE, Franke H. Involvement of GPR17 in Neuronal Fibre Outgrowth. International Journal of Molecular Sciences. 2021; 22(21):11683. https://doi.org/10.3390/ijms222111683

Chicago/Turabian Style

Braune, Max, Nico Scherf, Claudia Heine, Katja Sygnecka, Thanigaimalai Pillaiyar, Chiara Parravicini, Bernd Heimrich, Maria P. Abbracchio, Christa E. Müller, and Heike Franke. 2021. "Involvement of GPR17 in Neuronal Fibre Outgrowth" International Journal of Molecular Sciences 22, no. 21: 11683. https://doi.org/10.3390/ijms222111683

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