Regulation of glucose transporters in the brain of a transgenic Alzheimer’s (5XFAD) mouse model
Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
Early diagnosis of the neurodegenerative Alzheimer’s disease is a difficult and complicated task. To facilitate research and treatment of the disease, new and improved diagnostic techniques are being developed. Decreases in glucose uptake specifically in parieto-temporal lobe, posterior cingulate cortex and frontal areas of the human Alzheimer’s brain are well documented and detectable prior to memory impairments. This indicates that techniques for measurement of cerebral glucose uptake such as 18F-FDG-PET might have diagnostic capacity. It is not known if the decrease in glucose uptake is due to reduced expression of the glucose transporters GLUT1 and GLUT4 in the brain. The aim of this study was therefore to investigate if the expression of GLUT1 and GLUT4 decreases as plaques develop in the 5xFAD Alzheimer’s mouse model. Plaques are initially found in subiculum and retrosplenial cortex in the brain of 5xFAD mice and GLUT4 is mainly expressed in the hippocampus. Brain sections from 8, 16, 26, 39 and 52 weeks old wild type and 5xFAD mice showing these brain areas were therefore immunihistochemically stained for GLUT1 and GLUT4. Images were captured with a fluorescent microscope and GLUT1 expressing blood vessels and astrocytes were counted in the ImageJ software. Statistical significance of the age and genotype impact on expression of GLUT1 was tested with two-way ANOVA. Results showed a significant increase in the number of GLUT1 expressing blood vessels and astrocytes in the subiculum of 5xFAD mice compared to wild type mice possibly due to neuroinflammation causing astrocytes to increase in number and activation level. However GLUT1 was lacking correlation with age and plaque load. Furthermore the level of GLUT4 staining in CA1 increased with age of the mice and also with plaque load in the 5xFAD mice. There also seemed to be differences in the staining pattern of GLUT4 in CA1, which might be disease related. The expression of GLUT4 thus seems to correlate to the level of age- and AD-related memory impairments.
Place, publisher, year, edition, pages
2015. , 36 p.
Alzheimer's disease, Glucose transporter, GLUT1, GLUT4, hypometabolism
Pharmacology and Toxicology Physiology Neurosciences
IdentifiersURN: urn:nbn:se:uu:diva-259875OAI: oai:DiVA.org:uu-259875DiVA: diva2:845746
Subject / course
Master of Science Programme in Pharmacy
Chai, Siew, Associate Professor and NHMRC Senior Research Fellow
Hallberg, Mathias, Universitetslektor vid Institutionen för farmaceutisk biovetenskap