Project description:We characterize the brain infiltrating leukocyte (CD45high cells) in wild-type and 3xTg-AD mice, a transgenic model of Alzheimer's disease (AD).
Project description:We characterize the brain infiltrating leukocyte (CD45high cells) in wild-type and 3xTg-AD mice, a transgenic model of Alzheimer's disease (AD).
Project description:We characterize the meningeal leukocyte (CD45+ cells) in wild-type and 3xTg-AD mice, a transgenic model of Alzheimer's disease (AD).
Project description:ILC2 are potent producers of IL-5 and IL-13 and Th2 cytokines. We have found that 3xTg-AD mice exhibit diminished ILC2 numbers and functionality in the brain barriers. We have found through scRNA-seq that cultured brain ILC2 from 7 months old 3xTg-AD mice expressed significantly less IL-5 ane Areg but increased Gzma and Gzmb.
Project description:Transcriptional profiling of the microdissected SVZ from 7-month-old mice Adult neurogenesis is suppressed in the SVZ of 3xTg mice, a model of Alzheimer's disease. To better understand the underlying mechanisms of this suppression, the goals of this experiment were to compare the transcriptional profiles of the SVZ neural stem cell niche in 3xTg-AD mice versus strain controls. We used early middle-aged mice (7-months-old) rather than old mice, in order to identify genetic changes that are not caused secondarily to other degenerative changes occurring in these mice. Two-condition experiment, 3xTg vs WT SVZ. Biological replicates: 4 for each.
Project description:Repetitive mild traumatic brain injuries (rmTBI) sustained within a window of vulnerability can result in long term cognitive deficits, depression, and eventual neurodegeneration associated with tau pathology, amyloid beta plaques, gliosis, and neuronal and functional loss. However, we have limited understanding of how successive injuries affect the brain to result in these devastating long-term consequences. In the current study, we addressed the question of how repeated injuries affect the brain in the acute phase of injury (<24hr) by exposing the 3xTg-AD mouse model of tau and amyloid beta pathology to successive (1x, 3x, 5x) once-daily weight drop closed-head injuries and quantifying transcription at 30min, 4hr, and 24hr after each injury.
Project description:Background: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by memory impairment. Neuroinflammatory processes, mediated by glial and immune cells, contribute to neuronal damage. Emerging evidence implicates innate immune mechanisms, including trained immunity and cell trans-differentiation, in AD pathogenesis, though their roles remain unclear. Objective: To investigate transcriptomic changes in the 3xTg-AD mouse model, focusing on trained immunity and cell trans-differentiation in disease mechanisms. Methods: RNA-sequencing was performed on brain tissue (cortex plus hippocampus) from 11-month-old female 3xTg-AD and wild-type mice (n = 3/group). Differentially expressed genes (fold change > 1.5, p < 0.05) were identified and followed by bioinformatics and knowledge-based transcriptomic profiling. Public AD datasets were also analyzed. Results: 3xTg-AD mice exhibited 316 upregulated and 412 downregulated genes. Downregulated genes included those for blood-brain barrier protein, while upregulated genes related to cerebrospinal fluid. Increased expression of proinflammatory markers, as well as genes related to cell differentiation, proliferation, activation, and adhesion. Upregulation of genes associated with cell migration and trans-differentiation suggests a potential role for inflammation and cellular plasticity. Additionally, genes involved in inflammasome pathways, immunometabolism, and trained immunity were upregulated. Mechanistically, these genes were modulated by knockdown of trained immunity promoter SET-7, overexpression of trained immunity inhibitor IL-37, and knockout of inflammasome genes IL-1 receptor, caspase-1, and pattern recognition receptor CD36. Conclusions: The finding underscore the potential role of trained immunity and cell trans_x0002_differentiation in AD, revealing a mechanistic framework in which danger-associated molecular patterns drive innate immune responses, inflammasome activation, and cell plasticity contribute to AD, offering therapeutic targets for neuroinflammation and cellular reprograming.