Diet Supplementation with Hydroxytyrosol Ameliorates Brain Pathology and Restores Cognitive Functions in a Mouse Model of Amyloid-β Deposition

2018 ◽  
Vol 63 (3) ◽  
pp. 1161-1172 ◽  
Author(s):  
Pamela Nardiello ◽  
Daniela Pantano ◽  
Andrea Lapucci ◽  
Massimo Stefani ◽  
Fiorella Casamenti
Keyword(s):  
Mouse Model ◽  
Cognitive Functions ◽  
Amyloid Β ◽  
Brain Pathology ◽  
Diet Supplementation

scholarly journals Blood-Brain Barrier Disruption Increases Amyloid-Related Pathology in TgSwDI Mice

2021 ◽  
Vol 22 (3) ◽  
pp. 1231
Author(s):  
Ihab M. Abdallah ◽  
Kamal M. Al-Shami ◽  
Euitaek Yang ◽  
Amal Kaddoumi
Keyword(s):  
Mouse Model ◽  
Blood Brain Barrier ◽  
High Throughput Screening ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Amyloid Angiopathy ◽  
Cancer Resistance ◽  
Screening Assay ◽  
Blood Brain ◽  
High Throughput Screening Assay

In Alzheimer’s disease (AD), several studies have reported blood-brain barrier (BBB) breakdown with compromised function. P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are transport proteins localized at the BBB luminal membrane and play an important role in the clearance of amyloid-β (Aβ). The purpose of this study was to investigate the effect of pharmacological inhibition of Aβ efflux transporters on BBB function and Aβ accumulation and related pathology. Recently, we have developed an in vitro high-throughput screening assay to screen for compounds that modulate the integrity of a cell-based BBB model, which identified elacridar as a disruptor of the monolayer integrity. Elacridar, an investigational compound known for its P-gp and BCRP inhibitory effect and widely used in cancer research. Therefore, it was used as a model compound for further evaluation in a mouse model of AD, namely TgSwDI. TgSwDI mouse is also used as a model for cerebral amyloid angiopathy (CAA). Results showed that P-gp and BCRP inhibition by elacridar disrupted the BBB integrity as measured by increased IgG extravasation and reduced expression of tight junction proteins, increased amyloid deposition due to P-gp, and BCRP downregulation and receptor for advanced glycation end products (RAGE) upregulation, increased CAA and astrogliosis. Further studies revealed the effect was mediated by activation of NF-κB pathway. In conclusion, results suggest that BBB disruption by inhibiting P-gp and BCRP exacerbates AD pathology in a mouse model of AD, and indicate that therapeutic drugs that inhibit P-gp and BCRP could increase the risk for AD.

scholarly journals 24(S)-Saringosterol Prevents Cognitive Decline in a Mouse Model for Alzheimer’s Disease

Marine Drugs ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 190
Author(s):  
Nikita Martens ◽  
Melissa Schepers ◽  
Na Zhan ◽  
Frank Leijten ◽  
Gardi Voortman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Cognitive Decline ◽  
Inflammatory Marker ◽  
Amyloid Β ◽  
Liver Fat ◽  
Gas Chromatography Mass Spectrometry ◽  
Memory Decline ◽  
Plaque Load

We recently found that dietary supplementation with the seaweed Sargassum fusiforme, containing the preferential LXRβ-agonist 24(S)-saringosterol, prevented memory decline and reduced amyloid-β (Aβ) deposition in an Alzheimer’s disease (AD) mouse model without inducing hepatic steatosis. Here, we examined the effects of 24(S)-saringosterol as a food additive on cognition and neuropathology in AD mice. Six-month-old male APPswePS1ΔE9 mice and wildtype C57BL/6J littermates received 24(S)-saringosterol (0.5 mg/25 g body weight/day) (APPswePS1ΔE9 n = 20; C57BL/6J n = 19) or vehicle (APPswePS1ΔE9 n = 17; C57BL/6J n = 19) for 10 weeks. Cognition was assessed using object recognition and object location tasks. Sterols were analyzed by gas chromatography/mass spectrometry, Aβ and inflammatory markers by immunohistochemistry, and gene expression by quantitative real-time PCR. Hepatic lipids were quantified after Oil-Red-O staining. Administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice without affecting the Aβ plaque load. Moreover, 24(S)-saringosterol prevented the increase in the inflammatory marker Iba1 in the cortex of APPswePS1ΔE9 mice (p < 0.001). Furthermore, 24(S)-saringosterol did not affect the expression of lipid metabolism-related LXR-response genes in the hippocampus nor the hepatic neutral lipid content. Thus, administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice independent of effects on Aβ load and without adverse effects on liver fat content. The anti-inflammatory effects of 24(S)-saringosterol may contribute to the prevention of cognitive decline.

scholarly journals Impaired spike-gamma coupling of area CA3 fast-spiking interneurons as the earliest functional impairment in the AppNL-G-F mouse model of Alzheimer’s disease

2021 ◽  
Author(s):  
Luis Enrique Arroyo-García ◽  
Arturo G. Isla ◽  
Yuniesky Andrade-Talavera ◽  
Hugo Balleza-Tapia ◽  
Raúl Loera-Valencia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mouse Model ◽  
Functional Impairment ◽  
Amyloid Β ◽  
Gamma Oscillations ◽  
Gamma Oscillation ◽  
Gamma Rhythm ◽  
Fast Spiking

AbstractIn Alzheimer’s disease (AD) the accumulation of amyloid-β (Aβ) correlates with degradation of cognition-relevant gamma oscillations. The gamma rhythm relies on proper neuronal spike-gamma coupling, specifically of fast-spiking interneurons (FSN). Here we tested the hypothesis that decrease in gamma power and FSN synchrony precede amyloid plaque deposition and cognitive impairment in AppNL-G-F knock-in mice (AppNL-G-F). The aim of the study was to evaluate the amyloidogenic pathology progression in the novel AppNL-G-F mouse model using in vitro electrophysiological network analysis. Using patch clamp of FSNs and pyramidal cells (PCs) with simultaneous gamma oscillation recordings, we compared the activity of the hippocampal network of wild-type mice (WT) and the AppNL-G-F mice at four disease stages (1, 2, 4, and 6 months of age). We found a severe degradation of gamma oscillation power that is independent of, and precedes Aβ plaque formation, and the cognitive impairment reported previously in this animal model. The degradation correlates with increased Aβ1-42 concentration in the brain. Analysis on the cellular level showed an impaired spike-gamma coupling of FSN from 2 months of age that correlates with the degradation of gamma oscillations. From 6 months of age PC firing becomes desynchronized also, correlating with reports in the literature of robust Aβ plaque pathology and cognitive impairment in the AppNL-G-F mice. This study provides evidence that impaired FSN spike-gamma coupling is one of the earliest functional impairment caused by the amyloidogenic pathology progression likely is the main cause for the degradation of gamma oscillations and consequent cognitive impairment. Our data suggests that therapeutic approaches should be aimed at restoring normal FSN spike-gamma coupling and not just removal of Aβ.

Silymarin Attenuated the Amyloid β Plaque Burden and Improved Behavioral Abnormalities in an Alzheimer’s Disease Mouse Model

2010 ◽  
Vol 74 (11) ◽  
pp. 2299-2306 ◽  
Author(s):  
Nakaba MURATA ◽  
Kazuma MURAKAMI ◽  
Yusuke OZAWA ◽  
Noriaki KINOSHITA ◽  
Kazuhiro IRIE ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Amyloid Β ◽  
Plaque Burden ◽  
Behavioral Abnormalities

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 Effects of γ-Secretase Inhibition on the Amyloid β Isoform Pattern in a Mouse Model of Alzheimer’s Disease

2009 ◽  
Vol 6 (5-6) ◽  
pp. 258-262 ◽  
Author(s):  
Erik Portelius ◽  
Bin Zhang ◽  
Mikael K. Gustavsson ◽  
Gunnar Brinkmalm ◽  
Ann Westman-Brinkmalm ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Amyloid Β ◽  
Model Of Alzheimer’S Disease

scholarly journals Correlations of Behavioral Deficits with Brain Pathology Assessed through Longitudinal MRI and Histopathology in the R6/2 Mouse Model of HD

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e60012 ◽  
Author(s):  
Ivan Rattray ◽  
Edward Smith ◽  
Richard Gale ◽  
Kaoru Matsumoto ◽  
Gillian P. Bates ◽  
...  
Keyword(s):  
Mouse Model ◽  
Brain Pathology ◽  
Behavioral Deficits ◽  
Longitudinal Mri
Sign in / Sign up

Export Citation Format

Share Document