ABSTRACT: 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 report the binding between tRNA fragments and Phosphorylated Tau pS396 from the hippocampus of WT controls and Tau-mutant PS19 (human P301S Tau transgenic) mice. We show tRNA fragments abundance in Tau-RNA complexes changes between the two groups. Specific tRNA fragment in the results of Real Time-qPCR were consistent with the small RNA microarray:5'tRF_GluCTC
Project description:Aggregation of the microtubule-associated protein, tau, can lead to neurofibrillary tangle formation in neurons and glia, the hallmark of tauopathy. The cellular damages induced by the tau overexpression and aggregation may lead to multiple pathologic features of tauopathy. However, the effect of aging on tauopathy has not been elucidated yet. Here, we conducted lncRNA/mRNA sequencing analysis on P301S mutant Tau transgenic mouse model (PS19) with different ages to track the genetic changes occurred by the aging and progression of tau overexpression.
Project description:In this dataset, we evalute the effect of modulating the levels of LSD1 in the PS19 tauopathy mouse (mouse that expresses the P301S mutated form of the human tau transgene). First we reduced the levels of LSD1 by crossing PS19 Tau mice with mice heterozygous for Lsd1. This results in an exacerbation of the neurodegenerative phenotype as well as an increase in the transcripational changes observed in taupoathy mice. Secondy, we overexprssed LSD1 in neurons of the adult tauopathy mouse through viral injection direclty into the hippocampus. This resulted in a reduce of neuronal cell death as well as the associated transcriptional changes.
Project description:Tau Monomer from age controlled healthy and Alzheimer's Disease
LUM2_C10053
LUM2_C10054
LUM2_C10055
LUM2_C10056
LUM2_C10057
LUM2_C10058
Tau fibril from Alzheimer's Disease
LUM2_630897
Tau monomer from brain of PS19 mouse at age week 1, 2, 3, 4, 5, 6
LUM1_C11496 to LUM1_C11501
Tau monomer from brain of PS19 mouse at age 1 year
LUM1_705666
Project description:We performed RNA-sequencing of nontransgenic and transgenic By line of tau SPAM mice (expressing the S320F/P301S aggregating mutations) at different ages of 2, 4, and 6 months. All of the samples were obtained from brain cortex.
Project description:The purpose of this project was to compare whole genome expression in 5 transgenic mice with human genes for dementia that result in either plaques or tangle pathology to the expression in wild-type control mice and to each other at different stages of disease progression. Total RNA was obtained from hippocampus, cortex and cerebellum in four lines of ‘amyloid’ transgenic mice (mutant human APP and APP/PSEN1 genes) and ‘TAU’ transgenic mice (mutant human MAPT gene) as well as wild-type control mice at 8,16, 32 and 72 weeks
Project description:A role for the type I transmembrane trafficking receptor SORLA in reducing Aβ levels has been well-established, however, virtually nothing is known with respect to whether and how SORLA can potentially affect tau pathology. Here, we show that transgenic SORLA upregulation (SORLA TG) can reverse pathological effects in aged PS19 (P301S tau) mouse brain, including tau phosphorylation, ventricle dilation, synapse loss, LTP impairment and glial hyperactivation. Proteomic analysis indicates reversion of PS19 profiles in PS19/SORLA TG hippocampus, including pathological changes in synapse-related proteins as well as key drivers of synaptic dysfunction such as Apoe and C1q. snRNAseq analysis reveals suppression of PS19-dependent signatures with SORLA upregulation, including proinflammatory induction of Plxnb1/Plxnb2 in glial cell types. PlxnB1/B2 expression as well as other neuroinflammatory features are exacerbated in PS19 hippocampus with SORLA deletion. Together, these results implicate a global role for SORLA in neuroprotection from tau toxicity in PS19 mouse brain.
Project description:A role for the type I transmembrane trafficking receptor SORLA in reducing Aβ levels has been well-established, however, virtually nothing is known with respect to whether and how SORLA can potentially affect tau pathology. Here, we show that transgenic SORLA upregulation (SORLA TG) can reverse pathological effects in aged PS19 (P301S tau) mouse brain, including tau phosphorylation, ventricle dilation, synapse loss, LTP impairment and glial hyperactivation. Proteomic analysis indicates reversion of PS19 profiles in PS19/SORLA TG hippocampus, including pathological changes in synapse-related proteins as well as key drivers of synaptic dysfunction such as Apoe and C1q. snRNAseq analysis reveals suppression of PS19-dependent signatures with SORLA upregulation, including proinflammatory induction of Plxnb1/Plxnb2 in glial cell types. PlxnB1/B2 expression as well as other neuroinflammatory features are exacerbated in PS19 hippocampus with SORLA deletion. Together, these results implicate a global role for SORLA in neuroprotection from tau toxicity in PS19 mouse brain.