Project description:We performed snRNA-seq using 10xgenomics platform to study the role of MAIT cells in regulating neuroinflammation in mice with neurodegenerative tau pathology. MAIT cells are a type of innate-like T cells that are present in the meninges of mice carrying neurodgenerative human tau mutant transgene. This is the first study to examine single nucleus transcriptome profiles of human tau mice lacking MAIT cells.
Project description:The purpose of this experiment is to examine the cellular and molecular changes in the microglia and other non-neuron cells in the hippocampus of 7 month old Mr1+/+ and Mr1-/- mice.
Project description:We looked to find earlier molecular changes in 2-month-old transgenic P301S mice. S-nitrosylated (SNO) proteins were identified in two brain regions, cortex and hippocampus, in P301S and Wild Type (WT) littermate control mice.
Project description:Plaques are a hallmark feature of Alzheimer’s disease (AD). We found that the loss of mucosal-associated invariant T (MAIT) cells and its antigen-presenting molecule MR1 caused a delay in plaque pathology development in AD mouse models. However, it remains unknown how this axis is impacting dystrophic neurites. Brain tissue from 5XFAD mice and those that are MR1-deficient (MR1 KO), were analyzed for dystrophic neurites, amyloid plaques, and synapses via immunofluorescence, RNA sequencing, ELISA, and Western blot. In 8-month-old 5XFAD/MR1 KO mice, there was reduced expression of LAMP1, Ubiquitin, and n-terminal APP in the hippocampus as compared to 5XFAD mice (p < 0.05). 5XFAD/MR1 KO mice also had less insoluble Aβ40 (p < 0.001) and higher levels of PSD95 (p < 0.01) in the hippocampus. Our data contribute additional mechanistic insight into the detrimental role of the MR1/MAIT cell axis in AD pathology development.
Project description:We performed high-throughput snRNA-seq on hippocampus (Hip) and prefrontal lobe cortex (PFC) tissue in mice (Mus musculus) to identify cell-type specific differentially expressed genes. Mice were divided into GF, SPF and CGF group.
Project description:Mr1 knockout (Mr1−/−) mice, in which thymic cells lose the ability to promote the development of mature Mucosal-associated invariant T (MAIT) cells, induced systemic MAIT cell depletion. MAIT cells often exhibit altered functions during fibrosis and inflammatory diseases. Here we used intraperitoneal injections of 4.25% PD fluid (0.1 mL/g) daily for six weeks to mimic peritoneal dialysis (PD) related fibrosis in mice, and investigated whether Mr1 knockout could ameliorated PD-induced changes in peritoneal transcriptome. We analyzed bulk RNA-seq of peritoneums from Mr1+/+ + PBS group (n=3), Mr1+/+ + PD group (n=3), Mr1-/- + PBS group (n=2), and Mr1-/- + PD group (n=2), and demonstrated that Mr1 knockout could ameliorated PD-induced activation in fibrosis, hyperglycolysis, and mTORC1 signalings. In addition, the activation scores of these pathways are positively correlated with each other.
Project description:To assess the potential neuroprotective effects of overexpressing skeletal muscle Transcription Factor EB (TFEB) signaling in the context of age-associated neurodegenerative disease pathologies, we derived cTFEB;HSACre transgenic mice in the MAPT P301S tau hyperphosphorylated background and used the Nanostring nCounter® Alzheimer’s Disease panel to gain more precise insights into disease-relevant transcriptional changes in the hippocampus in both male and female mice with both Tau hyperphosphorylation and skeletal muscle TFEB overexpression. We confirmed significantly reduced transcriptional activation of the nCounter AD microglial activation module through signature scoring.