scholarly journals Dauricine Attenuates Spatial Memory Impairment and Alzheimer-Like Pathologies by Enhancing Mitochondrial Function in a Mouse Model of Alzheimer's Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Chongyang Chen ◽  
Pan Liu ◽  
Jing Wang ◽  
Haitao Yu ◽  
Zaijun Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tricarboxylic Acid Cycle ◽  
Therapeutic Effects ◽  
Hyperphosphorylated Tau ◽  
Mitochondrial Energy Metabolism ◽  
Model Of Alzheimer’S Disease ◽  
Amyloid Aβ ◽  
Vesicle Cycle ◽  
Related Proteins

Alzheimer's disease (AD) is characterized by extracellular amyloid plaques composed of β-amyloid (Aβ) and intracellular neurofibrillary tangles containing hyperphosphorylated tau protein. No effective therapy is available for this disease. In this study, we investigated the potential therapeutic effects of dauricine (DAU), a benzyl tetrahydroisoquinoline alkaloid, on AD, and found that DAU administration significantly improved cognitive impairments in 3xTg-AD mice by decreasing Aβ plaques and hyperphosphorylated tau and increasing the hippocampal ATP level. Proteomic and western blot analyses revealed that DAU treatment mainly modified the expression of proteins involved in mitochondrial energy metabolism, such as Aco2, Ndufs1, Cox5a, and SDHB, and that of synapse-related proteins such as Syn1 and Syn2. Pathway analysis revealed that DAU modulated the tricarboxylic acid cycle, synaptic vesicle cycle, glycolysis, and gluconeogenesis in 3xTg-AD mice. Our study suggests that DAU may be a potential drug for the treatment of AD.

scholarly journals P3-270: CHF5074 reduces brain β-amyloid burden and hyperphosphorylated tau in a mouse model of Alzheimer's disease

2009 ◽  
Vol 5 (4S_Part_14) ◽  
pp. P422-P422
Author(s):  
M. Pizzi ◽  
A. Lanzillotta ◽  
B.P. Imbimbo ◽  
B. Hutter-Paier ◽  
G. Villetti ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Hyperphosphorylated Tau ◽  
Amyloid Burden ◽  
Model Of Alzheimer’S Disease ◽  
Β Amyloid

scholarly journals Methionine sulfoxide reductase A affects β-amyloid solubility and mitochondrial function in a mouse model of Alzheimer's disease

2016 ◽  
Vol 310 (6) ◽  
pp. E388-E393 ◽  
Author(s):  
Jackob Moskovitz ◽  
Fang Du ◽  
Connor F. Bowman ◽  
Shirley S. Yan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Methionine Sulfoxide Reductase A ◽  
Model Of Alzheimer’S Disease ◽  
Amyloid Aβ ◽  
Β Amyloid

Accumulation of oxidized proteins, and especially β-amyloid (Aβ), is thought to be one of the common causes of Alzheimer's disease (AD). The current studies determine the effect of an in vivo methionine sulfoxidation of Aβ through ablation of the methionine sulfoxide reductase A (MsrA) in a mouse model of AD, a mouse that overexpresses amyloid precursor protein (APP) and Aβ in neurons. Lack of MsrA fosters the formation of methionine sulfoxide in proteins, and thus its ablation in the AD-mouse model will increase the formation of methionine sulfoxide in Aβ. Indeed, the novel MsrA-deficient APP mice ( APP+/ MsrAKO) exhibited higher levels of soluble Aβ in brain compared with APP+ mice. Furthermore, mitochondrial respiration and the activity of cytochrome c oxidase were compromised in the APP+/ MsrAKO compared with control mice. These results suggest that lower MsrA activity modifies Aβ solubility properties and causes mitochondrial dysfunction, and augmenting its activity may be beneficial in delaying AD progression.

scholarly journals Dopaminergic dysfunction in the 3xTg-AD mice model of Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yesica Gloria ◽  
Kelly Ceyzériat ◽  
Stergios Tsartsalis ◽  
Philippe Millet ◽  
Benjamin B. Tournier
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuropsychiatric Symptoms ◽  
Mice Model ◽  
Model Of Alzheimer’S Disease ◽  
Dopaminergic Dysfunction ◽  
Early Inflammatory Response ◽  
Hyper Sensitivity ◽  
Amyloid Aβ ◽  
Shed Light

AbstractAlzheimer’s disease (AD) is characterized by amyloid (Aβ) protein aggregation and neurofibrillary tangles accumulation, accompanied by neuroinflammation. With all the therapeutic attempts targeting these biomarkers having been unsuccessful, the understanding of early mechanisms involved in the pathology is of paramount importance. Dopaminergic system involvement in AD has been suggested, particularly through the appearance of dopaminergic dysfunction-related neuropsychiatric symptoms and an overall worsening of cognitive and behavioral symptoms. In this study, we reported an early dopaminergic dysfunction in a mouse model presenting both amyloid and Tau pathology. 3xTg-AD mice showed an increase of postsynaptic D2/3R receptors density in the striatum and D2/3-autoreceptors in SN/VTA cell bodies. Functionally, a reduction of anxiety-like behavior, an increase in locomotor activity and D2R hyper-sensitivity to quinpirole stimulation have been observed. In addition, microglial cells in the striatum showed an early inflammatory response, suggesting its participation in dopaminergic alterations. These events are observed at an age when tau accumulation and Aβ deposits in the hippocampus are low. Thus, our results suggest that early dopaminergic dysfunction could have consequences in behavior and cognitive function, and may shed light on future therapeutic pathways of AD.

scholarly journals Muramyl dipeptide mediated immunomodulation on monocyte subsets exerts therapeutic effects in a mouse model of Alzheimer’s disease

2020 ◽  
Author(s):  
Adham Fani Malekia ◽  
Giulia Cisbania ◽  
Marie-Michèle Plante ◽  
Paul Préfontaine ◽  
Nataly Laflamme ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Muramyl Dipeptide ◽  
Therapeutic Effects ◽  
Monocyte Subsets ◽  
Expression Levels ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
Model Of Alzheimer’S Disease

Abstract Background Muramyl dipeptide (MDP) is a component derived from minimal peptidoglycan motif from bacteria and it is a ligand for the NOD2 receptor. Peripheral administration of MDP converts Ly6Chigh into Ly6Clow monocytes. Previously we have shown that Ly6Clow monocytes play crucial roles in the pathology of a mouse model of Alzheimer’s disease (AD). However, medications with mild immunomodulatory effects that solely target specific monocyte subsets, without triggering microglial activation are rare. Methods 3-months old APPswe/PS1 transgenic male mice and age-matched C57BL/6J mice were used for high frequency (2-times/week) over 6-months and low frequency (once a week) over a 3-months period of intraperitoneally MDP (10 mg/kg) administrations. Flow cytometry analysis of monocyte subsets in blood, behavioral and post mortem analyses were performed. Two-photon microscopy using APP/PS1/CX3CR1gfp/+ mice were conducted to study vascular Aβ clearance by Ly6Clow monocytes upon MDP administration.Results The treatment improved cognitive declines, increased expression levels of postsynaptic density protein 95 (PSD95) andlow density lipoprotein receptor-related protein 1 (LRP1), which are involved in synaptic plasticity and amyloid beta (Aβ) elimination, respectively. In addition, we found monocyte chemoattractant protein-1(MCP-1) levels significantly increased, whereas intercellular adhesion molecule-1(ICAM-1) significantly decreased and microglial marker (Iba1) did not change in treatment group compared to the control. In parallel, we discovered elevated cyclooxygenase-2 (COX2) expression levels in the treated group, which might be a positive factor for synaptic activity. Following MDP treatment, intravital two-photon microscopy demonstrated that Ly6Clow monocytes are recruited into the brain vasculature in APP but not wild type mice, and they are able to pick up Aβ peptides. Conclusions Our results demonstrate that MDP is beneficial in both the early phase and to some extent later phases of the pathology in the mouse model of AD. These data open the way for potential MDP-based medications for AD.

scholarly journals Neurotrophin-3 Promotes the Neuronal Differentiation of BMSCs and Improves Cognitive Function in a Rat Model of Alzheimer's Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Zhongrui Yan ◽  
Xianjing Shi ◽  
Hui Wang ◽  
Cuiping Si ◽  
Qian Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Neuronal Differentiation ◽  
Molecular Mechanisms ◽  
Therapeutic Effects ◽  
Model Of Alzheimer’S Disease ◽  
Neurotrophin 3

Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) has the potential to be developed into an effective treatment for neurodegenerative diseases such as Alzheimer's disease (AD). However, the therapeutic effects of BMSCs are limited by their low neural differentiation rate. We transfected BMSCs with neurotrophin-3 (NT-3), a neurotrophic factor that promotes neuronal differentiation, and investigated the effects of NT-3 gene overexpression on the differentiation of BMSCs into neurons in vitro and in vivo. We further studied the possible molecular mechanisms. We found that overexpression of NT-3 promoted the differentiation of BMSCs into neurons in vitro and in vivo and improved cognitive function in rats with experimental AD. By contrast, silencing NT-3 inhibited the differentiation of BMSCs and decreased cognitive function in rats with AD. The Wnt/β-catenin signaling pathway was involved in the mechanism by which NT-3 gene modification influenced the neuronal differentiation of BMSCs in vitro and in vivo. Our findings support the prospect of using NT-3-transduced BMSCs for the development of novel therapies for AD.

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