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Analysis of neuronal transcripts of PGC-1α transgenic mice

Show simple item record 2013-07-02T12:00:09Z 2015-07-29T08:21:01Z 2013-07-02T12:00:09Z 2015-07-29T08:21:01Z 2013-07-02
dc.title Analysis of neuronal transcripts of PGC-1α transgenic mice en
ethesis.discipline Biochemistry en
ethesis.discipline Biokemia fi
ethesis.discipline Biokemi sv
ethesis.department Biomedicinska institutionen sv
ethesis.department Institute of Biomedicine en
ethesis.department Biolääketieteen laitos fi
ethesis.faculty Faculty of Medicine en
ethesis.faculty Medicinska fakulteten sv
ethesis.faculty Lääketieteellinen tiedekunta fi
ethesis.faculty.URI Helsingfors universitet sv University of Helsinki en Helsingin yliopisto fi
dct.creator Döhla, Julia Maria
dct.issued 2013
dct.language.ISO639-2 eng
dct.abstract Peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) is a transcriptional coactivator involved in mitochondrial biogenesis, oxidative stress response, and energy metabolism. PGC-1α is part of an energy sensing network that translates environmental influences into alterations in gene expression of mainly mitochondrial molecular pathways. A role in neuroprotection has been implicated for PGC-1α in the context of mitochondrial expression networks. Our research group has previously established a transgenic mouse line with stable overexpression of PGC-1α in brain neurons. Transgenic overexpression of PGC-1α is associated with an enhanced functional state of mitochondrial energy production. In the context of neurodegenerative processes, brain neurons of PGC-1α transgenic mice are protected against oxidative stressors in the MPTP mouse model of Parkinson's Disease. To further characterize the transcriptional activity of PGC-1α regulated gene networks in brains of transgenic mice, a quantitative real-time PCR based system was established. Gene expression was measured for a subset of genes found to be differentially regulated in a microarray based screening of RNA obtained from hippocampus and cortex of PGC-1α transgenic mice. Increased PGC-1α gene expression was found in hippocampus and cortex of PGC-1α transgenic mice, and their translation into protein was confirmed immunohistochemically. Expression analysis revealed significant changes in mRNA levels of PGC-1α controlled molecular pathways involved in mitochondrial energy production and antioxidant responses. Furthermore, alterations in the expression of some non-mitochondrial genes with established links to neurodegeneration were observed. Furthermore, a change in GABAA receptor subunit expression was detected. In accordance with previous studies on the PGC-1α transgenic mouse line, these findings suggest that differential gene expression associated with PGC-1α overexpression contributes to an enhanced functional state of neurons in hippocampus and cortex of PGC-1α transgenic mice. Increased knowledge about the transcriptional modulation of neuronal genes regulated by PGC-1α can lead to better insights into mechanisms governing neurodegeneration and neuroprotective pathways. Pharmacological modulation of PGC-1α activity may be a feasible approach for neuroprotective treatments in neurodegenerative diseases, such as Parkinson's Disease. en
dct.language en
ethesis.language English en
ethesis.language englanti fi
ethesis.language engelska sv
ethesis.supervisor Lindholm, Dan
ethesis.thesistype pro gradu-avhandlingar sv
ethesis.thesistype pro gradu -tutkielmat fi
ethesis.thesistype master's thesis en
dct.identifier.urn URN:NBN:fi:hulib-201507282459
dc.type.dcmitype Text
ethesis-internal.updated TRUE2

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