title: Glial Cell Line-Derived Neurotrophic Factor Family Members Reduce Microglial Activation via Inhibiting p38MAPKs-Mediated Inflammatory Responses.
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)).
authors: Department of Anatomy, University of Kiel, Olshausenstraße 40, 24098 Kiel, Germany.
authors: Uta
authors: U
authors: Rickert
authors: Department of Anatomy, University of Kiel, Olshausenstraße 40, 24098 Kiel, Germany ; Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nuernberg, 91054 Erlangen, Germany.
authors: Steffen
authors: S
authors: Grampp
authors: Department of Neurology, Texas Tech University, 3601 4th Street, Lubbock, TX 79430, USA.
authors: Henrik
authors: H
authors: Wilms
authors: Department of Anatomy, University of Kiel, Olshausenstraße 40, 24098 Kiel, Germany.
authors: Jessica
authors: J
authors: Spreu
authors: Department of Neurosurgery, University Hospital of Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
authors: Friederike
authors: F
authors: Knerlich-Lukoschus
authors: Department of Neurosurgery, University Hospital of Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
authors: Janka
authors: J
authors: Held-Feindt
authors: Department of Anatomy, University of Kiel, Olshausenstraße 40, 24098 Kiel, Germany.
authors: Ralph
authors: R
authors: Lucius