Publications by authors named "T Saido"
Background: Previously, we found that germline C3 deletion protected cognition and hippocampal synapses in aged APP/PS1dE9 mice, despite increasing Aß plaques. Here, we crossed our C3 inducible conditional mouse model to APP knockin mice to determine whether global C3 lowering in an adult amyloid mouse model would be protective.
Methods: C3;Rosa26-Cre-ERT2 (C3iKO) mice were crossed to C3;APP mice to generate APP;C3iKO mice, which received 75 mg/kg tamoxifen (TAM; n = 16) or corn oil (CO; n = 15) for 5 days at 3.
Tau pathology is a hallmark of several neurodegenerative diseases, including frontotemporal dementia and Alzheimer's disease. However, the sequence of events and the form of tau that confers toxicity are still unclear, due in large part to the lack of physiological models of tauopathy initiation and progression in which to test hypotheses. We have developed a series of targeted mice expressing frontotemporal-dementia-causing mutations in the humanized MAPT gene to investigate the earliest stages of tauopathy.
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- Researchers created a new Alzheimer’s disease (AD) model mouse using human tau protein to better understand microglial states related to tau pathology, which hasn't been thoroughly studied yet.
- The study found that microglia associated with disease increased after tau accumulation, suggesting a shift from age-related microglia to a disease-associated profile in the brains of these model mice.
- Advanced techniques like single-nucleus RNA sequencing and spatial transcriptomics were employed to highlight how tau propagation affects microglial behavior, paving the way for deeper insights into tau-related changes in the AD brain.
Article Synopsis
- Alzheimer's disease is marked by the buildup of amyloid β and tau proteins, leading to neuroinflammation primarily driven by activated glial cells, which worsens the condition.
- Researchers found that the cannabinoid receptor type II (Cnr2/Cb2) is upregulated in both mouse models of Alzheimer's and in human brain tissue affected by the disease, suggesting a potential therapeutic role.
- Administering JWH 133, a specific CB2 agonist, improved cognitive function in mice with Alzheimer's symptoms by reducing neuroinflammation and harmful astrocyte responses, indicating that targeting the CB2 receptor could be a promising strategy for treating Alzheimer's and other neurodegenerative diseases.
The physiological actions of a gut hormone, glucagon-like peptide-1 (GLP-1), in Alzheimer's disease (AD) brain remain poorly understood, although GLP-1 receptor (GLP-1R) expression in this organ has been shown in several experimental studies. Therefore, we explored whether the GLP-1R signaling promotes the clearance of amyloid β (Aβ) (1-42) which is a core pathological hallmark of AD, focusing on the water channel protein aquaporin 4 (AQP4) localized to astrocyte endfeet perivascular membranes in intact brain. First, we confirmed that Glp1r mRNA is predominantly expressed at perivascular site of astrocytes in normal mouse cerebral cortex through in situ hybridization analysis.
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