Glial Cell Line-Derived Neurotrophic Factor Family Members Reduce Microglial Activation via Inhibiting p38MAPKs-Mediated Inflammatory Responses

Journal of Neurodegenerative Diseases
Uta RickertRalph Lucius

Abstract

Previous studies have shown that glial cell line-derived neurotrophic factor (GDNF) family ligands (GFL) are potent survival factors for dopaminergic neurons and motoneurons with therapeutic potential for Parkinson's disease. However, little is known about direct influences of the GFL on microglia function, which are known to express part of the GDNF receptor system. Using RT-PCR and immunohistochemistrym we investigated the expression of the GDNF family receptor alpha 1 (GFR alpha) and the coreceptor transmembrane receptor tyrosine kinase (RET) in rat microglia in vitro as well as the effect of GFL on the expression of proinflammatory molecules in LPS activated microglia. We could show that GFL are able to regulate microglia functions and suggest that part of the well known neuroprotective action may be related to the suppression of microglial activation. We further elucidated the functional significance and pathophysiological implications of these findings and demonstrate that microglia are target cells of members of the GFL (GDNF and the structurally related neurotrophic factors neurturin (NRTN), artemin (ARTN), and persephin (PSPN)).

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Citations

Apr 8, 2020·Cells·Lucas MorelTatiana Michel
Sep 4, 2017·Molecular Neurobiology·Sara HernandoRosa Maria Hernandez
Jan 27, 2019·Journal of Molecular Neuroscience : MN·Jessica KronenbergMartin Stangel
Aug 21, 2018·Frontiers in Cellular Neuroscience·Diana MatiasVivaldo Moura-Neto
Sep 12, 2020·International Journal of Molecular Sciences·Yulia A Sidorova, Mart Saarma
Dec 12, 2019·Frontiers in Bioengineering and Biotechnology·Cristiana R CarvalhoRui L Reis
Jun 21, 2020·Neuroscience Letters·Ifeoluwa Oluleke AwogbindinMarie-Ève Tremblay

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Methods Mentioned

BETA
mechanical dissociation
FCS
fluorescence microscopy
PCR
ELISA

Software Mentioned

GraphPad Prism

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