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Glial cell line-der...
Glial cell line-derived neurotrophic factor is crucial for long-term maintenance of the nigrostriatal system
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- Nevalainen, Nina (författare)
- Umeå universitet,Histologi med cellbiologi
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- Chermenina, Maria (författare)
- Umeå universitet,Histologi med cellbiologi
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- Rehnmark, Anna (författare)
- Umeå universitet,Histologi med cellbiologi
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- Berglöf, Elisabeth (författare)
- Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB)
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- Marschinke, Franziska (författare)
- Umeå universitet,Histologi med cellbiologi
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- Strömberg, Ingrid (författare)
- Umeå universitet,Histologi med cellbiologi
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(creator_code:org_t)
- Elsevier, 2010
- 2010
- Engelska.
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Ingår i: Neuroscience. - : Elsevier. - 0306-4522 .- 1873-7544. ; 171:4, s. 1357-1366
- Relaterad länk:
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Nyckelord
- GDNF
- transplant
- substantia nigra
- striatum
- DARPP-32
- Gdnf knockout
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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