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Development of a cell culture model of Parkinson’s to examine HSPB5 function in LID/PD using a High-Content Imaging system
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2017 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Heat shock protein B5 HSPB5 is known as small heat shock protein with anti-inflammatory and neuroprotective functions, which is secreted via exosomes from oligodendrocytes. Recent studies have indicated that overexpression of HSPB5 plays a role in the development of levodopa-induced dyskinesia (LID).

The overall aim of this project was to evaluate a cell culture model of Parkinson’s disease and to study the function of HSPB5 in this model.

Primary cortical cell cultures were labeled with fluorescent markers and were analyzed with a high-content Imaging System after glutamate, dopamine and/or HSPB5 stimulation.

The results from 3-days stimulation with dopamine showed an increase of microtubule associated protein 2 (MAP2) immunoreactive neurons. In addition, live cell imaging during the first hour of stimulation indicated that dopamine stimulated glial cells to release exosomes containing HSPB5. Glutamate stimulation on primary cell cultures showed neurotoxicity on cells which indicated that the exposure time had been too long. The HSPB5 stimulation showed higher MAP2 immunoreactive intensity compared to other treatments but no other major differences were seen. Products of the fosB and pRS6 gene are causally related with the development of dyskinesia in the rat model of Parkinson’s disease and are often upregulated in the brain in response to chronic disorders. A higher number of FosB- and pRS6 immunoreactive cells could be seen one day compared to one week after stimulation with dopamine, similar to what has previously been seen in dyskinetic animals.

Overall, the results from this project indicate that the primary cell culture model respond in the same manner as seen in striatal neurons of dyskinetic rats.

 

Place, publisher, year, edition, pages
2017. , p. 30
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-336255OAI: oai:DiVA.org:uu-336255DiVA, id: diva2:1165516
Subject / course
Toxicology
Educational program
Master of Science Programme in Pharmacy
Supervisors
Examiners
Available from: 2017-12-19 Created: 2017-12-13 Last updated: 2017-12-19Bibliographically approved

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