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The Role of Glia Response in L-DOPA-induced Dyskinesia
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Toxicology.
2013 (English)Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Pakinson’s disease (PD) is a neurodegenerative disease which primarily treatment is substitution therapy with L-dopa. However, the drug is associated with the development of L-dopa induced dyskinesias (LID), which is more severe in some individuals. In this study we investigated proteomic changes in the striatum of low and high dyskinetic animals compared to control using the 6-OHDA rat model of PD. AMT (Accurate Mass and Time) tag mass spectrometry was used in order to detect proteomic changes which were then validated with fluorescent immunohistochemistry (IHC). The results from experiments in normal tissue strongly indicate that the CRYAB (αB-crystallin) immunoreactive (IR) cells are of oligodendrocyte lineage but not fully matured oligodendrocytes. The experiments in lesioned tissue display an upregulation of CRYAB in the high dyskinetic and control group, while the low dyskinetic group displayed a significant normalization in the lesioned striatum. GFAP (Glial Fibrillary Acidic Protein) was upregulated in the lesioned side compared to intact in all animals, indicating an increased number of astrocytes in the lesioned animals, which could be a consequence of the degeneration of the dopaminergic neurons. Our results suggest that the CRYAB-IR cells are oligodendrocytes that mature upon injury and that low levels of CRYAB is associated with less severe dyskinesia. 

Place, publisher, year, edition, pages
2013. , 24 p.
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-201443OAI: oai:DiVA.org:uu-201443DiVA: diva2:627368
Subject / course
Toxicology
Educational program
Master of Science Programme in Pharmacy
Supervisors
Examiners
Available from: 2013-06-11 Created: 2013-06-11 Last updated: 2013-06-11Bibliographically approved

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