Human apoB overexpression and a high-cholesterol diet differently modify the brain APP metabolism in the transgenic mouse model of atherosclerosis

2006 ◽  
Vol 49 (4) ◽  
pp. 393-400 ◽  
Author(s):  
Annamária Bjelik ◽  
Erika Bereczki ◽  
Szilvia Gonda ◽  
Anna Juhász ◽  
Ágnes Rimanóczy ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
App Metabolism ◽  
The Brain

scholarly journals Hypercholesterolemia and 27-Hydroxycholesterol Increase S100A8 and RAGE Expression in the Brain: a Link Between Cholesterol, Alarmins, and Neurodegeneration

2021 ◽  
Author(s):  
Raúl Loera-Valencia ◽  
Muhammad-Al-Mustafa Ismail ◽  
Julen Goikolea ◽  
Maria Lodeiro ◽  
Laura Mateos ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Primary Cultures ◽  
Transgenic Mouse Model ◽  
Intraventricular Injection ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
High Fat ◽  
The Brain ◽  
Rage Expression

AbstractAlterations in cholesterol metabolism in the brain have a major role in the physiology of Alzheimer’s disease (AD). Oxysterols are cholesterol metabolites with multiple implications in memory functions and in neurodegeneration. Previous studies have shown detrimental effects of cholesterol metabolites in neurons, but its effect in glial cells is unknown. We used a high-fat/high-cholesterol diet in mice to study the effects of hypercholesterolemia over the alarmin S100A8 cascade in the hippocampus. Using CYP27Tg, a transgenic mouse model, we show that the hypercholesterolemia influence on the brain is mediated by the excess of 27-hydroxycholesterol (27-OH), a cholesterol metabolite. We also employed an acute model of 27-OH intraventricular injection in the brain to study RAGE and S100A8 response. We used primary cultures of neurons and astrocytes to study the effect of high levels of 27-OH over the S100A8 alarmin cascade. We report that a high-fat/high-cholesterol diet leads to an increase in S100A8 production in the brain. In CYP27Tg, we report an increase of S100A8 and its receptor RAGE in the hippocampus under elevated 27-OH in the brain. Using siRNA, we found that 27-OH upregulation of RAGE in astrocytes and neurons is mediated by the nuclear receptor RXRγ. Silencing RXRγ in neurons prevented 27-OH-mediated upregulation of RAGE. These results show that S100A8 alarmin and RAGE respond to high levels of 27-OH in the brain in both neurons and astrocytes through RXRγ. Our study supports the notion that 27-OH mediates detrimental effects of hypercholesterolemia to the brain via alarmin signaling.

scholarly journals High-Cholesterol Diet Decreases the Level of Phosphatidylinositol 4,5-Bisphosphate by Enhancing the Expression of Phospholipase C (PLCβ1) in Rat Brain

2020 ◽  
Vol 21 (3) ◽  
pp. 1161 ◽  
Author(s):  
Yoon Sun Chun ◽  
Sungkwon Chung
Keyword(s):  
Neurodegenerative Diseases ◽  
Rat Brain ◽  
Phospholipase C ◽  
Cultured Cells ◽  
Cell Interaction ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Amyloid Aβ ◽  
The Brain

Cholesterol is a critical component of eukaryotic membranes, where it contributes to regulating transmembrane signaling, cell–cell interaction, and ion transport. Dysregulation of cholesterol levels in the brain may induce neurodegenerative diseases, such as Alzheimer’s disease, Parkinson disease, and Huntington disease. We previously reported that augmenting membrane cholesterol level regulates ion channels by decreasing the level of phosphatidylinositol 4,5-bisphosphate (PIP2), which is closely related to β-amyloid (Aβ) production. In addition, cholesterol enrichment decreased PIP2 levels by increasing the expression of the β1 isoform of phospholipase C (PLC) in cultured cells. In this study, we examined the effect of a high-cholesterol diet on phospholipase C (PLCβ1) expression and PIP2 levels in rat brain. PIP2 levels were decreased in the cerebral cortex in rats on a high-cholesterol diet. Levels of PLCβ1 expression correlated with PIP2 levels. However, cholesterol and PIP2 levels were not correlated, suggesting that PIP2 level is regulated by cholesterol via PLCβ1 expression in the brain. Thus, there exists cross talk between cholesterol and PIP2 that could contribute to the pathogenesis of neurodegenerative diseases.

Deletion of murine tau gene increases tau aggregation in a human mutant tau transgenic mouse model

2010 ◽  
Vol 38 (4) ◽  
pp. 1001-1005 ◽  
Author(s):  
Kunie Ando ◽  
Karelle Leroy ◽  
Céline Heraud ◽  
Anna Kabova ◽  
Zehra Yilmaz ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Double Mutant ◽  
Transgenic Mouse Model ◽  
Tau Proteins ◽  
Dependent Manner ◽  
Age Dependent ◽  
Ad Alzheimer’S Disease ◽  
Tau Aggregation ◽  
The Brain

We have reported previously a tau transgenic mouse model (Tg30tau) overexpressing human 4R1N double-mutant tau (P301S and G272V) and that develops AD (Alzheimer's disease)-like NFTs (neurofibrillary tangles) in an age-dependent manner. Since murine tau might interfere with the toxic effects of human mutant tau, we set out to analyse the phenotype of our Tg30tau model in the absence of endogenous murine tau with the aim to reproduce more faithfully a model of human tauopathy. By crossing the Tg30tau line with TauKO (tau-knockout) mice, we have obtained a new mouse line called Tg30×TauKO that expresses only exogenous human double-mutant 4R1N tau. Whereas Tg30×TauKO mice express fewer tau proteins compared with Tg30tau, they exhibit augmented sarkosyl-insoluble tau in the brain and an increased number of Gallyas-positive NFTs in the hippocampus. Taken together, exclusion of murine tau causes accelerated tau aggregation during aging of this mutant tau transgenic model.

Proteomic analysis of the brain tissues from a transgenic mouse model of amyloid β oligomers

2012 ◽  
Vol 61 (3) ◽  
pp. 347-355 ◽  
Author(s):  
Masaoki Takano ◽  
Kouji Maekura ◽  
Mieko Otani ◽  
Keiji Sano ◽  
Tooru Nakamura-Hirota ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Proteomic Analysis ◽  
Amyloid Β ◽  
Transgenic Mouse Model ◽  
The Brain ◽  
Brain Tissues

scholarly journals Pomegranate from Oman Alleviates the Brain Oxidative Damage in Transgenic Mouse Model of Alzheimer’s Disease

2014 ◽  
Vol 4 (4) ◽  
pp. 232-238 ◽  
Author(s):  
Selvaraju Subash ◽  
Musthafa Mohamed Essa ◽  
Abdullah Al-Asmi ◽  
Samir Al-Adawi ◽  
Ragini Vaishnav ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Oxidative Damage ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Model Of Alzheimer’S Disease ◽  
The Brain

scholarly journals Melatonin Treatment Enhances Aβ Lymphatic Clearance in a Transgenic Mouse Model of Amyloidosis

2018 ◽  
Vol 15 (7) ◽  
pp. 637-642 ◽  
Author(s):  
M.A. Pappolla ◽  
E. Matsubara ◽  
R. Vidal ◽  
J. Pacheco-Quinto ◽  
B. Poeggeler ◽  
...  
Keyword(s):  
Mouse Model ◽  
Lymph Nodes ◽  
Transgenic Mouse ◽  
Lymphatic System ◽  
Transgenic Mouse Model ◽  
Axillary Lymph ◽  
Prior Report ◽  
Aβ Aggregation ◽  
Aβ Clearance ◽  
The Brain

Background: It has been postulated that inadequate clearance of the amyloid β protein (Aβ) plays an important role in the accumulation of Aβ in sporadic late onset Alzheimer's disease (AD). While the blood brain barrier (BBB) has taken the center stage in processes involving Aβ clearance, little information is available about the role of the lymphatic system. We previously reported that Aβ is cleared through the lymphatic system. We now assessed lymphatic Aβ clearance by treating a mouse model of AD amyloidosis with melatonin, an Aβ aggregation inhibitor and immuno-regulatory neurohormone. Objective: To confirm and expand our initial finding that Aβ is cleared through the lymphatic system. Lymphatic clearance of metabolic and cellular “waste” products from the brain into the peripheral lymphatic system has been known for a long time. However, except for our prior report, there is no additional experimental data published about Aβ being cleared into peripheral lymph nodes. Methods: For these experiments, we used a transgenic mouse model (Tg2576) that over-expresses a mutant form of the Aβ precursor protein (APP) in the brain. We examined levels of Aβ in plasma and in lymph nodes of transgenic mice as surrogate markers of vascular and lymphatic clearance, respectively. Aβ levels were also measured in the brain and in multiple tissues. Results: Clearance of Aβ peptides through the lymphatic system was confirmed in this study. Treatment with melatonin led to the following changes: 1-A statistically significant increase in soluble monomeric Aβ40 and an increasing trend in Aβ42 in cervical and axillary lymph nodes of treated mice. 2- Statistically significant decreases in oligomeric Aβ40 and a decreasing trend Aβ42 in the brain. Conclusion: The data expands on our prior report that the lymphatic system participates in Aβ clearance from the brain. We propose that abnormalities in Aβ clearance through the lymphatic system may contribute to the development of cerebral amyloidosis. Melatonin and related indole molecules (i.e., indole- 3-propionic acid) are known to inhibit Aβ aggregation although they do not reverse aggregated Aβ or amyloid fibrils. Therefore, these substances should be further explored in prevention trials for delaying the onset of cognitive impairment in high risk populations.

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