Project description:Coffin–Lowry Syndrome (CLS) is a syndromic form of mental retardation caused by loss of function mutations in the X-linked RPS6KA3 gene, which encodes Rsk2, a serine/threonine kinase involved in spatial memory. We analyzed hippocampal gene expression profiles in Rsk2-KO mice to identify changes in molecular pathways. Total RNA was extracted from hippocampi from 6 KO and 6 WT (littermates) 2-month-old male mice. For each genotype, equivalent amounts of RNA from 2 mice were pooled and processed for hybridization to the genome wide oligonucleotide microarray (Murine 430A 2.0 Affymetrix, 22.000 probe sets). Thus, 3 independent pooled samples were hybridized for each genotype. We compared hippocampal gene expression profiles from rsk2-KO and normal littermate mice to identify changes in molecular pathways
Project description:Inhibition of soluble epoxide hydrolase (sEH) has been shown to suppress neuroinflammation through stabilizing epoxy fatty acids. Here we examined the role of sEH inhibitor TPPU in PS19 tauopathy mouse model by treating the 6-month-old wild-type and PS19 mice with vehicle or TPPU via drinking water continuously for 12 weeks, followed by performing single nucleus RNA-sequencing of the hippocampal tissues of the treated mice.
Project description:Coffin–Lowry Syndrome (CLS) is a syndromic form of mental retardation caused by loss of function mutations in the X-linked RPS6KA3 gene, which encodes Rsk2, a serine/threonine kinase involved in spatial memory. We analyzed hippocampal gene expression profiles in Rsk2-KO mice to identify changes in molecular pathways. Total RNA was extracted from hippocampi from 6 KO and 6 WT (littermates) 2-month-old male mice. For each genotype, equivalent amounts of RNA from 2 mice were pooled and processed for hybridization to the genome wide oligonucleotide microarray (Murine 430A 2.0 Affymetrix, 22.000 probe sets). Thus, 3 independent pooled samples were hybridized for each genotype.
Project description:Complement C3aR is primarily expressed in microglial cells in the brain. Our study found elevated expression of C3aR in microglia in Alzheimer's disease. To understand the underlying molecular mechanism, we sorted microglia based on their C3aR expression from 9-month-old wild-type and APP-KI mice. Through RNA-seq analysis, we identified metabolic perturbations in C3aR-positive microglia from 9-month-old APP-KI mice. Furthermore, we performed RNA-seq on sorted microglial cells from wild-type, C3aR knockout, APP-KI, and APP-KI;C3aR knockout mice. This analysis revealed a dampening of metabolic dysfunction in the absence of C3aR.
Project description:Expression of PS19 Tau Transgenic mice from hippocampus at different ages 3, 6, 9, and 12 months We used Affy arrays to understand the global expression profile of PS19 Tau transgenic mice
Project description:We analysed 3~4 repeats of 3 groups of mouse MII oocytes including 2-month-old WT, 2-month-old Tet2-KO, 11-month-old WT to find Tet2 function on female mice fertility.
Project description:Brain myeloid cells accumulate neutral lipids in multiple human neurodegenerative disorders and relevant mouse models. These lipid structures are often assumed to be lipid droplets (LDs), and ‘LD-high microglia’ have generally been characterized as maladaptive. While a number of studies have been performed in cell culture and Drosophila models to characterize glial LD dynamics, it is still unclear what roles microglial LD biogenesis play in mammalian tauopathy. To address this question, we induced the deletion of diacylglycerol acyltransferases 1 and 2 (DGATs), enzymes critical for LD formation, from microglia in the PS19 mouse model of tauopathy. We observed that microglial DGAT KO exacerbated neurodegeneration, induced behavioral deficits, and increased the accumulation of brain cholesterol esters in male PS19 mice. Myeloid cell lipids appeared to largely localize to endosomes/lysosomes not LDs, even in control PS19 mice. Our results suggest that microglial DGAT-dependent LD biogenesis is adaptive in advanced tauopathy. Furthermore, the bulk of the lipidic accumulations in brain myeloid cells do not correspond to true LDs, which has important implications for the development of lipid-modulating therapies for neurodegenerative diseases.
