An investigation of the role of insulin deficiency and loss of pi3k-akt signaling in the pathogenesis of the diabetic brain.
| atmire.migration.oldid | 259 | |
| dc.contributor.advisor | Toth, Cory | |
| dc.contributor.author | Derakhshan, Fatemeh | |
| dc.date.accessioned | 2012-08-30T18:59:43Z | |
| dc.date.available | 2012-11-13T08:01:24Z | |
| dc.date.issued | 2012-08-30 | |
| dc.date.submitted | 2012 | en |
| dc.description.abstract | Type 1 diabetes mellitus (DM) is associated with cognitive dysfunction, cerebral atrophy and white matter abnormalities composing diabetic leukoencephalopathy (DLE). Insulin deficiency contributes to these deficits and is amenable to replacement with intervention using intranasal insulin (I-I) delivery. An important insulin-mediated signalling pathway is propagated through phosphatidylinositol 3-kinase (PI3K) and Akt. We hypothesized that blockade of the PI3K-Akt pathway would prevent I-I’s beneficial effects in mice with DLE, and that this blockade would contribute to development of similar dysfunction in non-diabetic mice. Transgenic mice overexpressing cerebral Akt were expected to be protected from cognitive and white matter changes associated with DM. We interrogated the PI3K-Akt signalling pathway in a mouse model of Streptozotocin- induced type 1 DM over 7 months of life. Diabetic and non-diabetic mice received daily I-I (or intranasal-saline (I-S) for controls) concurrently with intranasal delivery of a PI3K inhibitor (Wortmannin) or an Akt inhibitor (API2). Mice were tested weekly for cognitive function, using a battery of behavioural tests, and endpoint magnetic resonance imaging (MRI). DM mice receiving I-I were protected from cognitive decline, while those mice receiving I-I along with either Wortmannin or API2 were subject to cognitive decline. Interestingly, non-DM mice receiving Wortmannin also developed significant cognitive dysfunction. Akt overexpressing transgenic diabetic mice were protected from cognitive decline. These results suggesting the importance of the PI3K-Akt pathway in DLE in the mouse model of DM. | en_US |
| dc.identifier.citation | Derakhshan, F. (2012). An investigation of the role of insulin deficiency and loss of pi3k-akt signaling in the pathogenesis of the diabetic brain. (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/24920 | en_US |
| dc.identifier.doi | http://dx.doi.org/10.11575/PRISM/24920 | |
| dc.identifier.uri | http://hdl.handle.net/11023/167 | |
| dc.language.iso | eng | |
| dc.publisher.faculty | Graduate Studies | |
| dc.publisher.institution | University of Calgary | en |
| dc.publisher.place | Calgary | en |
| dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | |
| dc.subject | Neuroscience | |
| dc.subject.classification | Diabetes | en_US |
| dc.subject.classification | Leukoencephalopathy | en_US |
| dc.subject.classification | Phosphatidylinositol 3-Kinases | en_US |
| dc.subject.classification | Intracellular Signaling Peptides and Proteins | en_US |
| dc.title | An investigation of the role of insulin deficiency and loss of pi3k-akt signaling in the pathogenesis of the diabetic brain. | |
| dc.type | master thesis | |
| thesis.degree.discipline | Neuroscience | |
| thesis.degree.grantor | University of Calgary | |
| thesis.degree.name | Master of Science (MSc) | |
| ucalgary.item.requestcopy | true |