date: 2021-10-28T11:24:56Z
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pdf:docinfo:title: Involvement of GPR17 in Neuronal Fibre Outgrowth
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Keywords: G protein-coupled receptor 17 (GPR17); neurite outgrowth; montelukast; NG2; ex vivo organotypic brain slice co-culture; neurodegeneration and neuroregeneration
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subject: 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.
dc:creator: Max Braune, Nico Scherf, Claudia Heine, Katja Sygnecka, Thanigaimalai Pillaiyar, Chiara Parravicini, Bernd Heimrich, Maria P. Abbracchio, Christa E. Müller and Heike Franke
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title: Involvement of GPR17 in Neuronal Fibre Outgrowth
Last-Save-Date: 2021-10-28T11:24:56Z
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pdf:docinfo:keywords: G protein-coupled receptor 17 (GPR17); neurite outgrowth; montelukast; NG2; ex vivo organotypic brain slice co-culture; neurodegeneration and neuroregeneration
pdf:docinfo:modified: 2021-10-28T11:24:56Z
meta:save-date: 2021-10-28T11:24:56Z
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dc:title: Involvement of GPR17 in Neuronal Fibre Outgrowth
modified: 2021-10-28T11:24:56Z
cp:subject: 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.
pdf:docinfo:subject: 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.
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pdf:docinfo:creator: Max Braune, Nico Scherf, Claudia Heine, Katja Sygnecka, Thanigaimalai Pillaiyar, Chiara Parravicini, Bernd Heimrich, Maria P. Abbracchio, Christa E. Müller and Heike Franke
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creator: Max Braune, Nico Scherf, Claudia Heine, Katja Sygnecka, Thanigaimalai Pillaiyar, Chiara Parravicini, Bernd Heimrich, Maria P. Abbracchio, Christa E. Müller and Heike Franke
meta:author: Max Braune, Nico Scherf, Claudia Heine, Katja Sygnecka, Thanigaimalai Pillaiyar, Chiara Parravicini, Bernd Heimrich, Maria P. Abbracchio, Christa E. Müller and Heike Franke
dc:subject: G protein-coupled receptor 17 (GPR17); neurite outgrowth; montelukast; NG2; ex vivo organotypic brain slice co-culture; neurodegeneration and neuroregeneration
meta:creation-date: 2021-10-28T11:21:25Z
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meta:keyword: G protein-coupled receptor 17 (GPR17); neurite outgrowth; montelukast; NG2; ex vivo organotypic brain slice co-culture; neurodegeneration and neuroregeneration
Author: Max Braune, Nico Scherf, Claudia Heine, Katja Sygnecka, Thanigaimalai Pillaiyar, Chiara Parravicini, Bernd Heimrich, Maria P. Abbracchio, Christa E. Müller and Heike Franke
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