| Author: | Cheung, Lung Chun |
| Title: | Investigation of the developmental deficits of oligodendrocytes in familial Alzheimer's disease model at the postnatal stage |
| Advisors: | Tse, K. H. Franki (HTI) |
| Degree: | M.Sc. |
| Year: | 2022 |
| Subject: | Alzheimer's disease Neuroglia Hong Kong Polytechnic University -- Dissertations |
| Department: | Department of Health Technology and Informatics |
| Pages: | 84 pages : color illustrations |
| Language: | English |
| Abstract: | Introduction: Familial Alzheimer's disease (AD) is characterized by early-onset Alzheimer disease due to gene mutations. It is an irreversible and progressive neurodegenerative disorder, leading to cognitive dysfunction, learning disability and memory impairment. Researchers have found that this form of the AD can result from mutations in the amyloid precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2) genes, causing the production of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) in human body, which have been considered as initial pathogenesis. Apart from the main hallmarks in AD, including Aβ plaques and NFTs, in the past two decades, many studies have revealed that the dysfunction in oligodendrocyte lineage cells is associated with myelin loss and PI3K/Akt/mTOR signalling pathway, and the latter is related to autophagy and apoptosis, and both processes take part in the AD pathogenesis. Because the effects of the therapeutic management targeting Aβ and NFTs were not ideal as discussed by many reviews, the treatment against the oligodendrocyte lineage cells and PI3K/Akt/mTOR signalling pathway could be as a new target. To date, there have been limited scientific evidence focusing on the effects of APP/PS1 mutation in the developmental change during the postnatal stage for oligodendrocyte lineage cells in familial AD mice model, the research project will investigate this aspect of interest. Aims: The research aims to study developmental change of the postnatal stage mice model with familial Alzheimer’s disease (amyloid precursor protein and presenilin 1 mutations) by using histological staining and molecular studies, so as to understand the pathogenesis of familial AD, especially the change in oligodendrocyte lineage cell, before the onset of any clinical symptoms, thereby hinting to the prevention of AD progression and thus the treatment. Method: Five postnatal day one male double transgenic AD house mice (Mus musculus, strain B6;C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax) with heterozygous APP/PS1 mutations and five postnatal day one male non-transgenic WT control mice were employed as the subjects for histological and molecular studies. The examination of the morphological change of the region of interest (ROI) was reviewed by Haemtoxylin & Eosin (HE) staining, including the hippocampus, cerebral cortex and white matter. Immunohistochemistry (IHC) staining for Olig2 and Nkx2.2 was conducted to compare the population change of oligodendrocyte lineage cells in ROI. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed to detect the change in gene expression of eight targeted genes (Mbp, Mag, Plp, Myrf, Akt1, Mtor, Lc3 and Bcl2), which are involved in the development and proliferation of oligodendrocyte lineage cells and/or PI3K/AKT/mTOR signalling pathway. Results: As observed in the HE sections, WT mice demonstrated the more numbers of cells per area than APP/PS1 mice in the three ROIs. APP/PS1 mice showed a higher positive rate and H-score of Olig2 than WT mice in IHC staining, whereas WT mice interestingly had a higher positive rate and H-score of Nkx2.2 than APP/PS1 mice. Regarding gene expression study, the gene expressions of the Mbp, Mag, Plp, Lc3, and Bcl2 showed higher relative expression in WT mice than APP/PS1 mice, and vice versa for the other three genes. Except the H-score of Olig2 in hippocampus, p values of other experiments were greater than 0.05, suggesting statistical non-significance. Conclusion: APP/PS1 mutations were significantly associated to the increase in population of the OPC and mature oligodendrocyte in hippocampus in P1 mice with respect to the Olig2 H-score results in hippocampus. It is considered as a possible repair mechanism from newly generated oligodendrocytes in APP/PS1 mice. Although most of the findings were not statistically significant because of the various limitations and technical issues in the experiments, it could still come as a revelation and foundation for other scientists in their future studies. |
| Rights: | All rights reserved |
| Access: | restricted access |
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| File | Description | Size | Format | |
|---|---|---|---|---|
| 6531.pdf | For All Users (off-campus access for PolyU Staff & Students only) | 4.04 MB | Adobe PDF | View/Open |
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