AFFITOPE®-based vaccination against C5a alleviates disease progression in a mouse model of Alzheimer's disease

Immunobiology ◽  
2012 ◽  
Vol 217 (11) ◽  
pp. 1136
Author(s):  
Christine Landlinger ◽  
Lisa Oberleitner ◽  
Petra Gruber ◽  
Markus Mandler ◽  
Frank Mattner ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Disease Progression ◽  
Model Of Alzheimer’S Disease

scholarly journals Disease Progression-Dependent Effects of TREM2 Deficiency in a Mouse Model of Alzheimer's Disease

2016 ◽  
Vol 37 (3) ◽  
pp. 637-647 ◽  
Author(s):  
Taylor R. Jay ◽  
Anna M. Hirsch ◽  
Margaret L. Broihier ◽  
Crystal M. Miller ◽  
Lee E. Neilson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Disease Progression ◽  
Model Of Alzheimer’S Disease

scholarly journals Disease Progression-Dependent Effects of TREM2 Deficiency in a Mouse Model of Alzheimer's Disease

2017 ◽  
Vol 37 (3) ◽  
pp. 637-647 ◽  
Author(s):  
Taylor R. Jay ◽  
Anna M. Hirsch ◽  
Margaret L. Broihier ◽  
Crystal M. Miller ◽  
Lee E. Neilson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Disease Progression ◽  
Model Of Alzheimer’S Disease

scholarly journals Astrocyte-neuron interplay is critical for Alzheimer’s disease pathogenesis and is rescued by TRPA1 channel blockade

2021 ◽  
Author(s):  
Adrien Paumier ◽  
Sylvie Boisseau ◽  
Karin Pernet-Gallay ◽  
Alain Buisson ◽  
Mireille Albrieux
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Disease Progression ◽  
Spatial Working Memory ◽  
Specific Inhibitor ◽  
Amyloid Β ◽  
Neuronal Dysfunction ◽  
Channel Activation ◽  
Model Of Alzheimer’S Disease

AbstractBackgroundThe sequence of cellular dysfunctions in preclinical Alzheimer’s disease must be understood if we are to plot new therapeutic routes. Hippocampal neuronal hyperactivity is one of the earliest events occurring during the preclinical stages of Alzheimer’s disease in both humans and mouse models. The most common hypothesis describes amyloid β accumulation as the triggering factor of the disease but the effects of such accumulation and the cascade of events leading to cognitive decline remain unclear. In mice, we previously showed that amyloid β-dependent TRPA1 channel activation triggers hippocampal astrocyte hyperactivity, subsequently inducing hyperactivity in nearby neurons. In this work, we investigated the potential protection brought by an early chronic pharmacological inhibition of TRPA1 channel on Alzheimer’s disease progression.MethodsWe administered a specific inhibitor of TRPA1 channel (HC030031) intraperitoneally from the onset of amyloid β overproduction in the APP/PS1-21 mouse model of Alzheimer’s disease. We characterized short-, medium-, and long-term effects of this chronic pharmacological TRPA1 blockade on Alzheimer’s disease progression at functional (astrocytic and neuronal activity), structural, biochemical, and behavioural levels.ResultsOur results revealed that the first observable disruptions in the Alzheimer’s disease transgenic mouse model used correspond to aberrant hippocampal astrocyte and neuron hyperactivity. We showed that chronic TRPA1 blockade normalizes astrocytic activity, avoids perisynaptic astrocytic process withdrawal, prevents neuronal dysfunction, preserves structural synaptic integrity and strengthens the glial plaque barrier. These protective effects preserved spatial working-memory in this Alzheimer’s disease mouse model.ConclusionThe toxic effect of amyloid β on astrocytes triggered by TRPA1 channel activation is pivotal to Alzheimer’s disease progression. TRPA1 blockade prevent irreversible neuronal dysfunction, making this channel a potential therapeutic target to promote neuroprotection.

scholarly journals Progressive impairments in executive function in the APP/PS1 model of Alzheimer’s disease as measured by translatable touchscreen testing

2019 ◽  
Author(s):  
A. Shepherd ◽  
J.K.H. Lim ◽  
V.H.Y. Wong ◽  
A.M. Zeleznikow-Johnston ◽  
L. Churilov ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
Mouse Model ◽  
Cognitive Decline ◽  
Disease Progression ◽  
Mouse Models ◽  
Preclinical Studies ◽  
Preclinical Models ◽  
Model Of Alzheimer’S Disease

AbstractExecutive function deficits in Alzheimer’s disease (AD) occur early in disease progression and may be predictive of cognitive decline. However, no preclinical studies have identified deficits in rewarded executive function in the commonly used APP/PS1 mouse model. To address this, we assessed 12-26 month old APP/PS1 mice on rewarded reversal and/or extinction tasks. 16-month-old, but not 13- or 26-month-old, APP/PS1 mice showed an attenuated rate of extinction. Reversal deficits were seen in 22-month-old, but not 13-month-old APP/PS1 animals. We then confirmed that impairments in reversal were unrelated to previously reported visual impairments in both AD mouse models and humans. Age, but not genotype, had a significant effect on markers of retinal health, indicating the deficits seen in APP/PS1 mice were directly related to cognition. This is the first characterisation of rewarded executive function in APP/PS1 mice, and has great potential to facilitate translation from preclinical models to the clinic.

scholarly journals Amelioration of Alzheimer’s Disease by Gut-Pancreas-Liver-Brain Interaction in an App Knock-In Mouse Model

Life ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 34
Author(s):  
Mayumi Minamisawa ◽  
Yuma Sato ◽  
Eitarou Ishiguro ◽  
Tetsuyuki Taniai ◽  
Taiichi Sakamoto ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Disease Progression ◽  
Bacterial Translocation ◽  
Bacterial Flora ◽  
Normal Diet ◽  
Model Of Alzheimer’S Disease ◽  
The Brain

In this study, we observed disease progression, changes in the gut microbiota, and interactions among the brain, liver, pancreas, and intestine in a mouse model of Alzheimer’s disease (AD), in addition to attempting to inhibit disease progression through the dietary supplementation of L-arginine and limonoids. Wild-type mice (WC) and AD mice were fed a normal diet (AC), a diet supplemented with L-arginine and limonoids (ALA), or a diet containing only limonoids (AL) for 12–64 weeks. The normal diet-fed WC and AC mice showed a decrease in the diversity of the gut microbiota, with an increase in the Firmicutes/Bacteroidetes ratio, and bacterial translocation. Considerable bacterial translocation to the pancreas and intense inflammation of the pancreas, liver, brain, and intestinal tissues were observed in the AC mice from alterations in the gut microbiota. The ALA diet or AL diet-fed mice showed increased diversity of the bacterial flora and suppressed oxidative stress and inflammatory responses in hepatocytes and pancreatic cells, bacterial translocation, and neurodegeneration of the brain. These findings suggest that L-arginine and limonoids help in maintaining the homeostasis of the gut microbiota, pancreas, liver, brain, and gut in AD mice.

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