GDNF is crucial for long-term maintenance of the nigrostriatal system
| Autor: | Nevalainen, Nina, Chermenina, Maria, Rehnmark, Anna, Berglöf, Elisabet, Marschinke, Franziska, Strömberg, Ingrid |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Time Factors
Tyrosine 3-Monooxygenase Cell Survival animal diseases Article Aldehyde Dehydrogenase 1 Family Mice Nerve Fibers Fetal Tissue Transplantation Neural Pathways Animals Glial Cell Line-Derived Neurotrophic Factor Mice Knockout Analysis of Variance urogenital system Retinal Dehydrogenase Aldehyde Dehydrogenase Embryo Mammalian Corpus Striatum Isoenzymes Mice Inbred C57BL Substantia Nigra nervous system G Protein-Coupled Inwardly-Rectifying Potassium Channels alpha-Synuclein Blood Vessels Microglia |
| Popis: | Glial cell line-derived neurotrophic factor (GDNF) is a potent factor for the ventral mesencephalic dopamine neurons. However, studies on the Gdnf gene deleted (Gdnf(-/-)) mouse have been limited to fetal tissue since these mice die prematurely. To evaluate long-term effects of Gdnf gene deletion, this study involves co-grafts of ventral mesencephalon (VM) and lateral ganglionic eminence (LGE) derived from different Gdnf genotypes. The VM/LGE co-grafts were evaluated at 3, 6, and 12 months for tyrosine hydroxylase (TH) -positive cell survival and nerve fiber formation in the LGE co-transplant, visualized by dopamine- and cyclic AMP-regulated phosphoprotein relative molecular mass 32,000 (DARPP-32) -immunoreactivity. Cell counts revealed no difference in TH-positive neurons between Gdnf genotypes at 3 months postgrafting. At 6 months, a significant reduction in cell number was observed in the Gdnf(-/-) grafts. In fact, in the majority of the Gdnf(-/-) VM/LGE transplant had degenerated. At 12 months, a reduction in cell number was seen in both Gdnf(-/-) and Gdnf(+/-) compared to wild type transplants. In the Gdnf(-/-) grafts, TH-negative inclusion-like structures were present in the cytoplasm of the TH-positive neurons at 3 months. These structures were also found in the Gdnf(+/-) transplants at 12 months, but not in Gdnf(+/+) controls at any time point. In Gdnf(+/+) grafts, TH-positive nerve fiber innervation of the striatal co-grafts was dense and patchy and overlapped with clusters of DARPP-32-positive neurons. This overlap did mismatch in the Gdnf(+/-) grafts, while the TH-positive innervation was sparse in the Gdnf(-/-) transplants and the DARPP-32-positive neurons were widespread distributed. In conclusion, GDNF is essential for long-term maintenance of both the VM TH-positive neurons and for the striatal tissue, and appears crucial for generation of a proper organization of the striatum. |
| Databáze: | OpenAIRE |
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