التفاصيل البيبلوغرافية
| العنوان: |
Growth/differentiation factor-15 deficiency compromises dopaminergic neuron survival and microglial response in the 6-hydroxydopamine mouse model of Parkinson's disease. |
| المؤلفون: |
Machado, Venissa1,2,3 venissa.machado@sgbm.uni-freiburg.de, Haas, Stefan J.-P.4 stefan.haas@uni-rostock.de, von Bohlen und Halbach, Oliver5 oliver.vonbohlen@uni-greifswald.de, Wree, Andreas4 andreas.wree@med.uni-rostock.de, Krieglstein, Kerstin1 kerstin.krieglstein@anat.uni-freiburg.de, Unsicker, Klaus1 ku39@anat.uni-freiburg.de, Spittau, Björn1 bjoern.spittau@anat.uni-freiburg.de |
| المصدر: |
Neurobiology of Disease. Apr2016, Vol. 88, p1-15. 15p. |
| مصطلحات موضوعية: |
*DOPAMINERGIC neurons, *NEUROGLIA, *GROWTH factors, *6-Hydroxydopamine, *PARKINSON'S disease, *ANIMAL models in research, *TRANSFORMING growth factors, *CYTOKINES |
| مستخلص: |
Growth/differentiation factor-15 (Gdf-15) is a member of the TGF-β superfamily and a pleiotropic, widely distributed cytokine, which has been shown to play roles in various pathologies, including inflammation. Analysis of Gdf-15 −/− mice has revealed that it serves the postnatal maintenance of spinal cord motor neurons and sensory neurons. In a previous study, exogenous Gdf-15 rescued 6-hydroxydopamine (6-OHDA) lesioned Gdf-15 +/+ nigrostriatal dopaminergic (DAergic) neurons in vitro and in vivo. Whether endogenous Gdf-15 serves the physiological maintenance of nigrostriatal DAergic neurons in health and disease is not known and was addressed in the present study. Stereotactic injection of 6-OHDA into the medial forebrain bundle (MFB) led to a significant decline in the numbers of DAergic neurons in both Gdf-15 +/+ and Gdf-15 −/− mice over a time-period of 14 days. However, this decrease was exacerbated in the Gdf-15 −/− mice, with only 5.5% surviving neurons as compared to 24% in the Gdf-15 +/+ mice. Furthermore, the microglial response to the 6-OHDA lesion was reduced in Gdf-15 −/− mice, with significantly lower numbers of total and activated microglia and a differential cytokine expression as compared to the Gdf-15 +/+ mice. Using in vitro models, we could demonstrate the importance of endogenous Gdf-15 in promoting DAergic neuron survival thus highlighting its relevance in a direct neurotrophic supportive role. Taken together, these results indicate the importance of Gdf-15 in promoting survival of DAergic neurons and regulating the inflammatory response post 6-OHDA lesion. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
