scholarly journals First effects of rising amyloid-β in transgenic mouse brain: synaptic transmission and gene expression

Brain ◽  
2015 ◽  
Vol 138 (7) ◽  
pp. 1992-2004 ◽  
Author(s):  
Damian M. Cummings ◽  
Wenfei Liu ◽  
Erik Portelius ◽  
Sevinç Bayram ◽  
Marina Yasvoina ◽  
...  
Keyword(s):  
Gene Expression ◽  
Synaptic Transmission ◽  
Transgenic Mouse ◽  
Mouse Brain ◽  
Amyloid Β

Specific Uptake of an Amyloid-β Protofibril-Binding Antibody-Tracer in AβPP Transgenic Mouse Brain

2013 ◽  
Vol 37 (1) ◽  
pp. 29-40 ◽  
Author(s):  
Kristina Magnusson ◽  
Dag Sehlin ◽  
Stina Syvänen ◽  
Marie M. Svedberg ◽  
Ola Philipson ◽  
...  
Keyword(s):  
Transgenic Mouse ◽  
Mouse Brain ◽  
Amyloid Β ◽  
Specific Uptake ◽  
Binding Antibody

scholarly journals 25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner

2020 ◽  
Author(s):  
Man Ying Wong ◽  
Michael Lewis ◽  
James J Doherty ◽  
Yang Shi ◽  
Anil G Cashikar ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Brain Tissue ◽  
Transgenic Mouse ◽  
Mouse Brain ◽  
Amyloid Β ◽  
Genome Wide Association Studies ◽  
Dependent Manner ◽  
Tau Pathology ◽  
Caspase 1 ◽  
Primary Mouse

Abstract Background : Genome-wide association studies of Alzheimer’s disease (AD) have implicated pathways related to lipid homeostasis and innate immunity in AD pathophysiology. However, the exact cellular and chemical mediators of neuroinflammation in AD remain poorly understood. The oxysterol 25-hydroxycholesterol (25-HC) is an important immunomodulator produced by peripheral macrophages with wide-ranging effects on cell signaling and innate immunity. Genetic variants of the enzyme responsible for 25-HC production, cholesterol 25‑hydroxylase (CH25H), have been found to be associated with AD. Methods: We used real time-PCR and immunoblotting to examine CH25H expression in human AD brain tissue and in transgenic mouse brain tissue bearing amyloid-β plaques or tau pathology. The innate immune response of primary mouse microglia under different treatment condition or bearing different genetic backgrounds was analyzed using ELISA, western blotting or immunocytochemistry. Results : We found that CH25H expression is upregulated in human AD brain tissue and in transgenic mouse brain tissue bearing amyloid-β plaques or tau pathology. Treatment with the toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS) markedly upregulates CH25H expression in the mouse brain and stimulates CH25H expression and 25-HC secretion in mouse primary microglia. We found that LPS-induced microglial production of the pro-inflammatory cytokine IL-1β is markedly potentiated by 25-HC and attenuated by deletion of CH25H. Microglia expressing apolipoprotein E4 (apoE4), a genetic risk factor for AD, produce greater amounts of 25-HC than apoE3-expressing microglia following treatment with LPS. Remarkably, 25-HC treatment results in a greater level of IL-1β secretion in LPS-activated apoE4-expressing microglia than in apoE2- or apoE3-expressing microglia. Blocking potassium efflux or inhibiting caspase-1 prevents 25-HC-potentiated IL-1β release in apoE4-expressing microglia, indicating the involvement of caspase-1/NLRP3 inflammasome activity. Conclusion : 25-HC may function as a microglial secreted inflammatory mediator in brain, promoting IL-1β-mediated neuroinflammation in an apoE isoform-dependent manner (E4>>E2/E3) and thus may be an important mediator of neuroinflammation in AD.

Gene expression profiling of the tau mutant (P301L) transgenic mouse brain

2001 ◽  
Vol 310 (1) ◽  
pp. 1-4 ◽  
Author(s):  
Lap Ho ◽  
Zhongmin Xiang ◽  
Piali Mukherjee ◽  
Wen Zhang ◽  
Nidia De Jesus ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Transgenic Mouse ◽  
Mouse Brain ◽  
Expression Profiling

scholarly journals Publisher Correction: nAChRs gene expression and neuroinflammation in APPswe/PS1dE9 transgenic mouse

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chiara D’Angelo ◽  
Erica Costantini ◽  
Nieves Salvador ◽  
Michele Marchioni ◽  
Marta Di Nicola ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transgenic Mouse

scholarly journals Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yuen Gao ◽  
Natalia Duque-Wilckens ◽  
Mohammad B. Aljazi ◽  
Yan Wu ◽  
Adam J. Moeser ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Brain ◽  
Molecular Mechanisms ◽  
Gene Mutations ◽  
Autism Spectrum ◽  
Normal Brain ◽  
Critical Function ◽  
Developmental Defects ◽  
Neurodevelopmental Disease ◽  
Developing Mouse Brain

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disease associated with various gene mutations. Recent genetic and clinical studies report that mutations of the epigenetic gene ASH1L are highly associated with human ASD and intellectual disability (ID). However, the causality and underlying molecular mechanisms linking ASH1L mutations to genesis of ASD/ID remain undetermined. Here we show loss of ASH1L in the developing mouse brain is sufficient to cause multiple developmental defects, core autistic-like behaviors, and impaired cognitive memory. Gene expression analyses uncover critical roles of ASH1L in regulating gene expression during neural cell development. Thus, our study establishes an ASD/ID mouse model revealing the critical function of an epigenetic factor ASH1L in normal brain development, a causality between Ash1L mutations and ASD/ID-like behaviors in mice, and potential molecular mechanisms linking Ash1L mutations to brain functional abnormalities.

scholarly journals Uncovering Statistical Links Between Gene Expression and Structural Connectivity Patterns in the Mouse Brain

2021 ◽  
Author(s):  
Nestor Timonidis ◽  
Alberto Llera ◽  
Paul H. E. Tiesinga
Keyword(s):  
Gene Expression ◽  
Mouse Brain ◽  
Structural Connectivity ◽  
Enrichment Analysis ◽  
Underlying Mechanism ◽  
Synaptic Function ◽  
Reticular Nucleus ◽  
Sources Of Information ◽  
Independent Components ◽  
Brain Connectome

AbstractFinding links between genes and structural connectivity is of the utmost importance for unravelling the underlying mechanism of the brain connectome. In this study we identify links between the gene expression and the axonal projection density in the mouse brain, by applying a modified version of the Linked ICA method to volumetric data from the Allen Institute for Brain Science for identifying independent sources of information that link both modalities at the voxel level. We performed separate analyses on sets of projections from the visual cortex, the caudoputamen and the midbrain reticular nucleus, and we determined those brain areas, injections and genes that were most involved in independent components that link both gene expression and projection density data, while we validated their biological context through enrichment analysis. We identified representative and literature-validated cortico-midbrain and cortico-striatal projections, whose gene subsets were enriched with annotations for neuronal and synaptic function and related developmental and metabolic processes. The results were highly reproducible when including all available projections, as well as consistent with factorisations obtained using the Dictionary Learning and Sparse Coding technique. Hence, Linked ICA yielded reproducible independent components that were preserved under increasing data variance. Taken together, we have developed and validated a novel paradigm for linking gene expression and structural projection patterns in the mouse mesoconnectome, which can power future studies aiming to relate genes to brain function.

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