| Dissertation |
Thesis (M.Sc.) --NUI, 2012 at Department of Anatomy, UCC. |
| Summary |
Parkinson's Disease is one of the most prevalent neurodegenerative diseases, involving the progressive loss of discreet dopaminergic neurons in the midbrain. Inflammation is currently being investigated as a driving force in the pathology of this disease. Current treatments ameliorate symptoms but do nothing to halt disease progression. Cell replacement therapy using tissue grown in vitro to replace cells lost in Parkinson's Disease presents a possible, more permanent treatment. Nurr1 is a key dopaminergic transcription factor which has recently been demonstrated to have an anti-inflammatory role. This study sought to further elucidate Nurr1's role in inflammation and any implications this could have for cell replacement therapies. Cells from the ventral mesencephalon of embryonic rats were treated with Tnfa under a variety of conditions. It was demonstrated that the expression of Nurr1 and the TNF receptors change over time in proliferation. A high dose of Tnfa was observed to be capable of increasing its own receptor expression and apoptotic cell death. A peak of Nurr1 expression was observed after 24 h of proliferation, at which a low dose of Tnfa was unable to affect Nurr1 expression. Nurr1 expression in neural stem cells was increased by a high dose of Tnfa but was decreased by a low dose after 2 h, possibly highlighting two separate pathways for Tnfa and Nurr1 interaction. A low dose, but not a high dose, of Tnfa for 2 h increased Nurr1 expression in dopaminergic neurons and reduced the percentage of dopaminergic neurons in cultures. This demonstrates a possible window of effectiveness of Tnfa concentration for affecting dopaminergic neurons. Overall this project demonstrates that Nurr1 reacts to inflammation differently in different phenotypes, and is important to consider in cell replacement therapy, with the varying levels of Nurr1 during proliferation could indicate an optimum time for transplantation of cells. |
| Subject |
Anatomy.
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| Collection |
Theses Masters
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Theses Anatomy Department
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| Description |
120 p. : ill. ; 30 cm. |
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