Table of Contents
Journal of Neurodegenerative Diseases
Volume 2014, Article ID 369468, 10 pages
http://dx.doi.org/10.1155/2014/369468
Research Article

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

1Department of Anatomy, University of Kiel, Olshausenstraße 40, 24098 Kiel, Germany
2Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nuernberg, 91054 Erlangen, Germany
3Department of Neurology, Texas Tech University, 3601 4th Street, Lubbock, TX 79430, USA
4Department of Neurosurgery, University Hospital of Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany

Received 3 April 2014; Accepted 18 May 2014; Published 9 June 2014

Academic Editor: Colin Combs

Copyright © 2014 Uta Rickert et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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)).