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 <i>ex v...

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Autores principales:	Max Braune, Nico Scherf, Claudia Heine, Katja Sygnecka, Thanigaimalai Pillaiyar, Chiara Parravicini, Bernd Heimrich, Maria P. Abbracchio, Christa E. Müller, Heike Franke
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	G protein-coupled receptor 17 (GPR17) neurite outgrowth montelukast NG2 <i>ex vivo</i> organotypic brain slice co-culture neurodegeneration and neuroregeneration Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/f02a609b008746deb0d3c435e46d1e1c
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spelling	oai:doaj.org-article:f02a609b008746deb0d3c435e46d1e1c2021-11-11T17:08:39ZInvolvement of GPR17 in Neuronal Fibre Outgrowth10.3390/ijms2221116831422-00671661-6596https://doaj.org/article/f02a609b008746deb0d3c435e46d1e1c2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11683https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Characterization 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 <i>ex vivo</i> 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.Max BrauneNico ScherfClaudia HeineKatja SygneckaThanigaimalai PillaiyarChiara ParraviciniBernd HeimrichMaria P. AbbracchioChrista E. MüllerHeike FrankeMDPI AGarticleG protein-coupled receptor 17 (GPR17)neurite outgrowthmontelukastNG2<i>ex vivo</i> organotypic brain slice co-cultureneurodegeneration and neuroregenerationBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11683, p 11683 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	G protein-coupled receptor 17 (GPR17) neurite outgrowth montelukast NG2 <i>ex vivo</i> organotypic brain slice co-culture neurodegeneration and neuroregeneration Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	G protein-coupled receptor 17 (GPR17) neurite outgrowth montelukast NG2 <i>ex vivo</i> organotypic brain slice co-culture neurodegeneration and neuroregeneration Biology (General) QH301-705.5 Chemistry QD1-999 Max Braune Nico Scherf Claudia Heine Katja Sygnecka Thanigaimalai Pillaiyar Chiara Parravicini Bernd Heimrich Maria P. Abbracchio Christa E. Müller Heike Franke Involvement of GPR17 in Neuronal Fibre Outgrowth
description	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 <i>ex vivo</i> 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.
format	article
author	Max Braune Nico Scherf Claudia Heine Katja Sygnecka Thanigaimalai Pillaiyar Chiara Parravicini Bernd Heimrich Maria P. Abbracchio Christa E. Müller Heike Franke
author_facet	Max Braune Nico Scherf Claudia Heine Katja Sygnecka Thanigaimalai Pillaiyar Chiara Parravicini Bernd Heimrich Maria P. Abbracchio Christa E. Müller Heike Franke
author_sort	Max Braune
title	Involvement of GPR17 in Neuronal Fibre Outgrowth
title_short	Involvement of GPR17 in Neuronal Fibre Outgrowth
title_full	Involvement of GPR17 in Neuronal Fibre Outgrowth
title_fullStr	Involvement of GPR17 in Neuronal Fibre Outgrowth
title_full_unstemmed	Involvement of GPR17 in Neuronal Fibre Outgrowth
title_sort	involvement of gpr17 in neuronal fibre outgrowth
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f02a609b008746deb0d3c435e46d1e1c
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Involvement of GPR17 in Neuronal Fibre Outgrowth

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