Involvement of GPR17 in neuronal fibre outgrowth

Abstract: 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

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch
Notes
International journal of molecular sciences. - 22, 21 (2021) , 11683, ISSN: 1422-0067

Event
Veröffentlichung
(where)
Freiburg
(who)
Universität
(when)
2021
Creator
Braune, Max
Scherf, Nico
Heine, Claudia
Sygnecka, Katja
Pillaiyar, Thanigaimalai
Parravicini, Chiara
Heimrich, Bernd
Abbracchio, Maria Pia
Müller, Christa E.
Franke, Heike

DOI
10.3390/ijms222111683
URN
urn:nbn:de:bsz:25-freidok-2226198
Rights
Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
15.08.2025, 7:34 AM CEST

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Associated

Time of origin

  • 2021

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