LE3 .A278 2010

2010

Wilson, Brian

Acadia University

Bachelor of Science

Honours

Biology

Biology

Parkinson’s disease is a neurodegenerative disorder that affects the dopaminergic neurons of the substantia nigra. The drug L- 3,4- dihydroxyphenylalanine ( L- DOPA) is the gold standard for the treatment of Parkinson’s disease but is accompanied by the development of dyskinesias. Neural transplantation has been proposed as a treatment for Parkinson’s disease; however, clinical trials have revealed that a number of patients also develop dyskinesias following transplantation. The serotonergic system has been implicated in the development of dyskinesias. This study examined the importance of the ratio of serotonergic cells to dopaminergic cells in a neural transplant on dyskinesias using a model of the fetal rat brain created for this purpose. Neurolucida ® was used to trace and label fetal brains for dopaminergic and serotonergic cells, and then to stack the images in a three- dimensional model. Dyskinesias were induced in hemiparkinsonian rats. Animals then received neural transplants rich in dopaminergic cells, rich in serotonergic cells, or containing a mixture of both cell types. Animals that received grafts rich in dopaminergic cells showed nearly complete recovery from parkinsonian behaviors and a significant reduction in dyskinesias compared to controls. Animals that received grafts rich in serotonin- producing cells or mixed grafts showed significant reduction in dyskinesias from pre- transplantation scores, but not compared to controls. The results suggest that although a cell ratio of 4: 1 dopaminergic cells to serotonergic cells is sufficient to effect recovery from dyskinesias and parkinsonism, recovery is maximized by grafts rich in dopaminergic cells.

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https://scholar.acadiau.ca/islandora/object/theses:713