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Neuroinflammation is mediated by activated microglia, the chief immune response of the central nervous system. Mitochondrial 18kDa translocator protein (TSPO) is upregulated in activated microglia and has been used in PET scans to analyze peripheral and central inflammation with TSPO radioligand [18F]DPA-714. To test the hypothesis that TSPO is involved

Neuroinflammation is mediated by activated microglia, the chief immune response of the central nervous system. Mitochondrial 18kDa translocator protein (TSPO) is upregulated in activated microglia and has been used in PET scans to analyze peripheral and central inflammation with TSPO radioligand [18F]DPA-714. To test the hypothesis that TSPO is involved in microglial mediation of inflammatory responses to Aβ and other Alzheimer’s pathological elements, TSPO expression was evaluated in relation to microglia specific markers (IBA1 and LN3 antibodies) and markers for AD pathology, Aβ (6E10 antibody) and hyperphosphorylated tau (AT8 antibody). To test that TSPO is involved in inflammatory pathways, HEK cells transfected with TSPO plasmids were assessed for oxidative stress in response to Alzheimer’s disease pathogenic agents, β Amyloid (Aβ), and Parkinson’s disease α-synuclein (α-syn).

Fluorescence microscopy of TSPO transfected HEK cell cultures labeled with Carboxy-H2DCFDA and treated with Beta Amyloid (Aβ) and α-synuclein (α-syn) resulted in DAPI fluorescing Human Embryonic Kidney (HEK) nuclei in blue and Green Fluorescent Protein (GFP) fluorescing reactive oxygen species (ROS) or oxidative stress in cell cytoplasm in green. Preliminary study suggests TSPO transfected cells may be used to test oxidative stress with disease pathological elements (Aβ and α-synuclein). In IHC, TSPO immunoreactivity was observed in IBA1 and LN3 marked microglia with varying degrees of expression. Beaded structures were also observed with TSPO immunoreactivities, possibly representing microglia processes. TSPO immunoreactivity was observed in and surrounding amyloid plaques and p-tau immunoreactive neurites. This demonstrates that TSPO is predominantly expressed in microglia and are closely associated with Alzheimer’s disease pathological elements, suggesting involvement of TSPO-expressing microglia in neurodegenerative processes.
ContributorsWu, Michael (Author) / Lue, Lih-Fen (Thesis director) / Washo-Krupps, Delon (Committee member) / School of Life Sciences (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description

This meta-study analyzes the shift in research literature that focuses on the various shared causes of type 2 diabetes and Alzheimer’s disease from the years 2000 to 2022. Examining literature trends over the past two decades can offer valuable insight into the evolving emphasis on various topics. Altogether, a total

This meta-study analyzes the shift in research literature that focuses on the various shared causes of type 2 diabetes and Alzheimer’s disease from the years 2000 to 2022. Examining literature trends over the past two decades can offer valuable insight into the evolving emphasis on various topics. Altogether, a total of 154 publications were collected from the Pubmed and ResearchGate databases using a non-biased protocol and methodology. Each paper was then categorized by the topics it discussed. Visual representation of the data such as bar graphs and tables were created to comprehend the trends presented in the group of papers. The collection of publications were then differentiated into years of early (prior to 2005 or 2010) and late (after 2006 or 2011) periods to perform a statistical analysis of the patterns in the timeline. The increase in publications discussing Alzheimer’s disease, amyloid beta deposition, gut microbiota, mitochondrial dysfunction, type 2 diabetes, and tau hyperphosphorylation from the early to the late period were statistically significant. This means that the increase was not due to random chance, but rather supported by evidence. This can be attributed to researchers and physicians discovering more evidence that establishes a link between specific factors, type 2 diabetes, and Alzheimer’s disease. This reflects a genuine acknowledgment of the importance of understanding and addressing the relationship between these two pathologies. Research in the trends of literature can provide information in which areas of research are the most studied or understudied. Based on these findings, the identification of areas with limited knowledge and potential research directions can be inferred, ultimately leading to the enhancement of preventive measures and therapeutic approaches for these conditions.

ContributorsShah, Khushi (Author) / Bang, Christofer (Thesis director) / Washo-Krupps, Delon (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2023-05