The normal aging process in humans is characterized by a number of hallmark changes including decreased white matter volume in the brain and accompanying cognitive decline. This is in contrast to neurodegenerative aging processes which involve acute pathology which results in neuronal cell death. Studying non-degenerative normal aging in humans can be difficult because of the high prevalence of neurodegenerative diseases in the population and other potentially confounding effects. Rhesus monkeys are an excellent model organism for the study of normal aging, as their aging process has been demonstrated to involve diminished white matter volume, but they do not suffer from neurodegenerative diseases such as Alzheimer's. In this study we seek to quantify levels of myelin degradation using confocal microscopy in regions of interest where it has been previously demonstrated that loss of white matter integrity results in lower levels of cognitive function across different treatment groups including aging monkeys, calorie restricted monkeys, and controls for calorie restricted monkeys. These areas include prefrontal white matter which is vital to executive function, the hippocampus which is integral to memory consolidation and the learning process, and finally the anterior, middle, and posterior cingulum bundle. The cingulum bundle contains a diverse variety of projections between cortical and subcortical regions, including but not limited to projections to and from the cingulate cortex which has been demonstrated to be vital for emotional processing, the limbic system, and a wide spectrum of other functions. We aim to quantify white matter degradation in these regions by using immunofluorescent tagging for healthy myelin basic protein (MBP) and degraded myelin basic protein (dMBP) and by measuring the colocalization between the two. For prefrontal white matter and hippocampus, we did not find significant differences in myelin degradation across treatment groups. In the cingulum bundle, however, we did find a significant effect of treatment on overall myelin damage throughout the bundle, and in particular we determined that there was a significant difference in colocalization in the anterior cingulum bundle between aging monkeys and control calorie restricted monkeys. Analysis of behavioral testing data yielded surprising results as we were unable to find a strong correlation between our measure for myelin degradation, and level of cognitive impairment. Our results indicate that there are likely differences in regional vulnerability to age related myelin damage across different white matter regions of the brain, however we would like to expand on this study to gain a more accurate understanding of how loss of white matter volume is distributed through the brain and the impact that has on cognitive outcomes.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/48224 |
| Date | 26 February 2024 |
| Creators | Haque, Haroun Ihsan |
| Contributors | Mortazavi, Farzad, Rosene, Douglas L. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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