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dc.contributor.supervisorXie, Jiuyong (Physiology and Pathophysiology)en_US
dc.contributor.authorGhandizadeh Dezfouli, Maryam
dc.date.accessioned2018-01-12T14:19:57Z
dc.date.available2018-01-12T14:19:57Z
dc.date.issued2018
dc.identifier.urihttp://hdl.handle.net/1993/32818
dc.description.abstractObjective: One of the key steps of the regulation of gene expression is alternative splicing of pre-mRNA. Previous studies have shown that alternative splicing is critical for adaptive changes of cells to repeated stimulation or stress. However, the underlying mechanisms of alternative splicing during these changes remain elusive. In this study we aim to identify the different effects of repeated versus single stimulation on the transcript abundance or alternative splicing of particular genes. Method: Effect of a single exposure or repeated dopamine (DA) or KCl treatment on the transcript abundance or alternative splicing of FosB in striatal cells was examined using RT-PCR. Moreover, to determine the changes of other candidate genes in this treatment scheme, RNA-Seq was carried out on the striatal cells treated with DA. Results: While changes in splicing variants of FosB was evident after KCl or DA stimulation, there was no difference in changes observed after a single exposure or after repeated treatment with KCl or DA. RNA-Seq data showed that the splicing factor cluster of genes was the most significant group that changed in alternative splicing after repeated DA treatment compared with non-treated (NT) cells. The transcription factor cluster, was most significantly changed for splice variation after a single exposure to KCl or DA. A similar difference was seen between repeated exposure and single exposure condition. In addition, with respect to transcript abundance, there were unique signatures of gene clusters affected by either single exposure or repeated exposure treatment. Conclusion: Alternative splicing of FosB does not change after repeated compared to first stimulation by KCl or DA. However, RNA-Seq reveals that repeated stimulation affects the expression, particularly alternative splicing of specific genes differently from that observed for a single stimulation.en_US
dc.language.isoengen_US
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectAlternative Splicingen_US
dc.subjectDopamineen_US
dc.subjectKCl-induced Depolarizationen_US
dc.subjectRNA-Seqen_US
dc.subjectFosBen_US
dc.titleStudying the adaptive changes of transcript abundance or splice variants upon repeated stimulation by KCl-induced depolarization or by dopamineen_US
dc.typeinfo:eu-repo/semantics/masterThesis
dc.typemaster thesisen_US
dc.degree.disciplinePhysiology and Pathophysiologyen_US
dc.contributor.examiningcommitteeDavie, Jim (Biochemistry and Medical Genetics) Halayko, Andrew (Physiology and Pathophysiology) Mishra, Suresh (Physiology and Pathophysiology)en_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.noteFebruary 2018en_US


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