scholarly journals The Impact of Ag Nanoparticles and CdTe Quantum Dots on Expression and Function of Receptors Involved in Amyloid-β Uptake by BV-2 Microglial Cells

Materials ◽  
2020 ◽  
Vol 13 (14) ◽  
pp. 3227
Author(s):  
Katarzyna Sikorska ◽  
Iwona Grądzka ◽  
Iwona Wasyk ◽  
Kamil Brzóska ◽  
Tomasz M. Stępkowski ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Cell Surface ◽  
Specific Inhibitor ◽  
Amyloid Β ◽  
Microglial Cells ◽  
Polyinosinic Acid ◽  
And Function ◽  
The Impact ◽  
The Brain ◽  
Cd36 Gene

Microglial cells clear the brain of pathogens and harmful debris, including amyloid-β (Aβ) deposits that are formed during Alzheimer’s disease (AD). We studied the expression of Msr1, Ager and Cd36 receptors involved in Aβ uptake and expression of Cd33 protein, which is considered a risk factor in AD. The effect of silver nanoparticles (AgNP) and cadmium telluride quantum dots (CdTeQD) on the expression of the above receptors and Aβ uptake by microglial cells was investigated. Absorption of Aβ and NP was confirmed by confocal microscopy. AgNP, but not CdTeQD, caused a decrease in Aβ accumulation. By using a specific inhibitor—polyinosinic acid—we demonstrated that Aβ and AgNP compete for scavenger receptors. Real-time PCR showed up-regulation of Cd33 and Cd36 gene expression after treatment with CdTeQD for 24 h. Analysis of the abundance of the receptors on the cell surface revealed that AgNP treatment significantly reduced the presence of Msr1, Cd33, Ager and Cd36 receptors (6 and 24 h), whereas CdTeQD increased the levels of Msr1 and Cd36 (24 h). To summarize, we showed that AgNP uptake competes with Aβ uptake by microglial cells and consequently can impair the removal of the aggregates. In turn, CdTeQD treatment led to the accumulation of proinflammatory Cd36 protein on the cell surface.

scholarly journals Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3261
Author(s):  
Xiao Liu ◽  
Qian Zhou ◽  
Jia-He Zhang ◽  
Xiaoying Wang ◽  
Xiumei Gao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Disease Model ◽  
Amyloid Β ◽  
Brain Lesions ◽  
Synaptic Dysfunction ◽  
Synaptic Loss ◽  
And Function ◽  
The Brain

Alzheimer’s disease (AD), the most common form of dementia, is characterized by amyloid-β (Aβ) accumulation, microglia-associated neuroinflammation, and synaptic loss. The detailed neuropathologic characteristics in early-stage AD, however, are largely unclear. We evaluated the pathologic brain alterations in young adult App knock-in model AppNL-G-F mice at 3 and 6 months of age, which corresponds to early-stage AD. At 3 months of age, microglia expression in the cortex and hippocampus was significantly decreased. By the age of 6 months, the number and function of the microglia increased, accompanied by progressive amyloid-β deposition, synaptic dysfunction, neuroinflammation, and dysregulation of β-catenin and NF-κB signaling pathways. The neuropathologic changes were more severe in female mice than in male mice. Oral administration of dioscin, a natural product, ameliorated the neuropathologic alterations in young AppNL-G-F mice. Our findings revealed microglia-based sex-differential neuropathologic changes in a mouse model of early-stage AD and therapeutic efficacy of dioscin on the brain lesions. Dioscin may represent a potential treatment for AD.

scholarly journals Regulatory Roles of Bone in Neurodegenerative Diseases

2020 ◽  
Vol 12 ◽  
Author(s):  
Zhengran Yu ◽  
Zemin Ling ◽  
Lin Lu ◽  
Jin Zhao ◽  
Xiang Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
The Elderly ◽  
Lymphoid Organ ◽  
The Body ◽  
Hematopoietic Stem ◽  
Brain Functions ◽  
And Function ◽  
The Impact ◽  
The Brain

Osteoporosis and neurodegenerative diseases are two kinds of common disorders of the elderly, which often co-occur. Previous studies have shown the skeletal and central nervous systems are closely related to pathophysiology. As the main structural scaffold of the body, the bone is also a reservoir for stem cells, a primary lymphoid organ, and an important endocrine organ. It can interact with the brain through various bone-derived cells, mostly the mesenchymal and hematopoietic stem cells (HSCs). The bone marrow is also a place for generating immune cells, which could greatly influence brain functions. Finally, the proteins secreted by bones (osteokines) also play important roles in the growth and function of the brain. This article reviews the latest research studying the impact of bone-derived cells, bone-controlled immune system, and bone-secreted proteins on the brain, and evaluates how these factors are implicated in the progress of neurodegenerative diseases and their potential use in the diagnosis and treatment of these diseases.

Diminished amyloid-β uptake by mouse microglia upon treatment with quantum dots, silver or cerium oxide nanoparticles: Nanoparticles and amyloid-β uptake by microglia

2019 ◽  
Vol 39 (2) ◽  
pp. 147-158 ◽  
Author(s):  
K Sikorska ◽  
I Grądzka ◽  
B Sochanowicz ◽  
A Presz ◽  
S Męczyńska-Wielgosz ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Cerium Oxide ◽  
Amyloid Β ◽  
Brain Cell ◽  
Cerium Oxide Nanoparticles ◽  
Oxide Nanoparticles ◽  
Progressive Dementia ◽  
Cytokine Tumor Necrosis Factor ◽  
Factor Α ◽  
The Brain

Alzheimer’s disease (AD) is a chronic neurodegenerative disease leading to progressive dementia in elderly people. The disease is characterized, among others, by formation of amyloid- β (A β) polypeptide plaques in the brain. Although etiology of the disease is not fully understood, recent research suggest that nanomaterials may affect AD development. Here, we described the consequences of exposure of mouse BV-2 microglia to silver nanoparticles (AgNPs, 50 µg/mL), cerium oxide nanoparticles (CeO2NPs, 100 µg/mL), and cadmium telluride quantum dots (CdTeQDs, 3 or 10 µg/mL) in the context of its ability to clear A β plaques. The brain microglial cells play an important role in removing A β plaques from the brain. Cell viability and cycle progression were assessed by trypan blue test and propidium iodide binding, respectively. The uptake of A β and NPs was measured by flow cytometry. Secretion of proinflammatory cytokines was measured with the use of cytometric bead array. A β (0.1 μM) did not affect viability, whereas NPs decreased microglia growth by arresting the cells in G1 phase (CdTeQDs) or in S phase (AgNPs and CeO2NPs) of cell cycle. The uptake of A β was significantly reduced in the presence of AgNPs and CeO2NPs. In addition, the least toxic CeO2NPs induced the release of proinflammatory cytokine, tumor necrosis factor α. In summary, each of the NPs tested affected either the microglia phagocytic activity (AgNPs and CeO2NPs) and/or its viability (AgNPs and CdTeQDs) that may favor the occurrence of AD and accelerate its development.

scholarly journals Expression and function of Abcg4 in the mouse blood-brain barrier: role in restricting the brain entry of amyloid-β peptide

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Agnès Dodacki ◽  
Matthew Wortman ◽  
Bruno Saubaméa ◽  
Stéphanie Chasseigneaux ◽  
Sophie Nicolic ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Amyloid Β Peptide ◽  
Mouse Blood ◽  
Blood Brain ◽  
And Function ◽  
The Brain

scholarly journals The Impact of Meditation on the Cognitive Functions of Patients with Alzheimer’s Disease

2021 ◽  
Author(s):  
Maria Clara Lopes Rezende ◽  
Mariana Vanon Moreira ◽  
Bárbara Gomes Muffato ◽  
Yves Henrique Faria Dias ◽  
Ana Luíza Badini Tubenchlak ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Function ◽  
Brain Network ◽  
Brain Structure And Function ◽  
Improve Sleep Quality ◽  
And Function ◽  
The Impact ◽  
The Brain ◽  
Positive Effect

Introduction: Alzheimer’s disease (AD) is the most common form of dementia, which has no cure and, also, effective therapies to prevent or slow the progression of AD remain elusive. Thus, it is necessary to find another way to treat this disease Objective: Investigate the impact of meditation on the cognitive function of patients with AD. Methods: In April 2021, a systematic review was carried out on MEDLINE using the descriptors: “Meditation” and “Alzheimer Disease” and their variations. Studies published in the last 10 years and in English were included. Results: Of the 40 articles found, four are part of this review. It was showed that meditation generates improvements in memory as it increases cerebral blood flow, stabilizes synapses and elevates important neurotransmitters. Aligned, it can improve sleep quality and retrospective memory function. Furthermore, daily practices help in neuropsychological conditions and generate beneficial changes in brain structure and function. Finally, it provokes changes in the brain network, such as the increased power of the theta band, involved in memory processes. Conclusion: The results imply a positive effect of meditation on patients with AD. However, further research is needed to confirm the validity of the results.

scholarly journals Mathematical model shows how sleep may affect amyloid β fibrillization

2019 ◽  
Author(s):  
Masoud Hoore ◽  
Sahamoddin Khailaie ◽  
Ghazal Montaseri ◽  
Tanmay Mitra ◽  
Michael Meyer-Hermann
Keyword(s):  
Mathematical Model ◽  
Production Rate ◽  
Amyloid Β ◽  
Cellular Level ◽  
Long Time ◽  
Diseased State ◽  
Aβ Fibers ◽  
The Impact ◽  
The Brain ◽  
Good Sleep

AbstractDeposition of amyloid β (Aβ) fibers in extra-cellular matrix of the brain is a ubiquitous feature associated with several neurodegenerative disorders, especially Alzheimer’s disease (AD). While many of the biological aspects that contribute to the formation of Aβ plaques are well addressed at the intra- and inter-cellular level in short timescales, an understanding of how Aβ fibrillization usually starts to dominate at a longer timescale in spite of the presence of mechanisms dedicated to Aβ clearance, is still lacking. Furthermore, no existing mathematical model integrates the impact of diurnal neural activity as emanated from circadian regulation to predict disease progression due to a disruption in sleep-wake cycle. In this study, we develop a minimal model of Aβ fibrillization to investigate the onset of AD over a long time-scale. Our results suggest that the diseased state is a manifestation of a phase change of the system from soluble Aβ (sAβ) to fibrillar Aβ (fAβ) domination upon surpassing a threshold in the production rate of soluble Aβ. By incorporating the circadian rhythm into our model, we reveal that fAβ accumulation is crucially dependent on the regulation of sleep-wake cycle, thereby indicating the importance of a good sleep hygiene in averting AD onset. We also discuss potential intervention schemes to reduce fAβ accumulation in the brain by modification of the critical sAβ production rate.

Mechanistic Modeling of Soluble Aβ Dynamics and Target Engagement in the Brain by Anti-Aβ mAbs in Alzheimer’s Disease

2020 ◽  
Vol 17 (4) ◽  
pp. 393-406
Author(s):  
Gregory Z. Ferl ◽  
Reina N. Fuji ◽  
Jasvinder K. Atwal ◽  
Tony Sun ◽  
Saroja Ramanujan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Mechanistic Modeling ◽  
Model Parameters ◽  
Target Engagement ◽  
Binding Characteristics ◽  
The Impact ◽  
The Brain

Background: Anti-amyloid-β (Aβ) monoclonal antibodies (mAbs) are currently in development for treating Alzheimer’s disease. Objectives: To address the complexity of Aβ target engagement profiles, improve the understanding of crenezumab Pharmacokinetics (PK) and Aβ Pharmacodynamics (PD) in the brain, and facilitate comparison of anti-Aβ therapies with different binding characteristics. Methods: A mechanistic mathematical model was developed describing the distribution, elimination, and binding kinetics of anti-Aβ mAbs and Aβ (monomeric and oligomeric forms of Aβ1-40 and Aβ1-42) in the brain, Cerebrospinal Fluid (CSF), and plasma. Physiologically meaningful values were assigned to the model parameters based on the previous data, with remaining parameters fitted to clinical measurements of Aβ concentrations in CSF and plasma, and PK/PD data of patients undergoing anti-Aβ therapy. Aβ target engagement profiles were simulated using a Monte Carlo approach to explore the impact of biological uncertainty in the model parameters. Results: Model-based estimates of in vivo affinity of the antibody to monomeric Aβ were qualitatively consistent with the previous data. Simulations of Aβ target engagement profiles captured observed mean and variance of clinical PK/PD data. Conclusion: This model is useful for comparing target engagement profiles of different anti-Aβ therapies and demonstrates that 60 mg/kg crenezumab yields a significant increase in Aβ engagement compared with lower doses of solanezumab, supporting the selection of 60 mg/kg crenezumab for phase 3 studies. The model also provides evidence that the delivery of sufficient quantities of mAb to brain interstitial fluid is a limiting step with respect to the magnitude of soluble Aβ oligomer neutralization.

scholarly journals Restoring Wnt/β-catenin signaling is a promising therapeutic strategy for Alzheimer’s disease

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Lin Jia ◽  
Juan Piña-Crespo ◽  
Yonghe Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rational Design ◽  
Signal Transduction Pathway ◽  
Amyloid Β ◽  
Synaptic Loss ◽  
Cellular Processes ◽  
And Function ◽  
The Brain ◽  
Blood Brain Barrier Integrity

AbstractAlzheimer’s disease (AD) is an aging-related neurological disorder characterized by synaptic loss and dementia. Wnt/β-catenin signaling is an essential signal transduction pathway that regulates numerous cellular processes including cell survival. In brain, Wnt/β-catenin signaling is not only crucial for neuronal survival and neurogenesis, but it plays important roles in regulating synaptic plasticity and blood-brain barrier integrity and function. Moreover, activation of Wnt/β-catenin signaling inhibits amyloid-β production and tau protein hyperphosphorylation in the brain. Critically, Wnt/β-catenin signaling is greatly suppressed in AD brain via multiple pathogenic mechanisms. As such, restoring Wnt/β-catenin signaling represents a unique opportunity for the rational design of novel AD therapies.

scholarly journals Astrocytes in Down Syndrome Across the Lifespan

2021 ◽  
Vol 15 ◽  
Author(s):  
Blandine Ponroy Bally ◽  
Keith K. Murai
Keyword(s):  
Down Syndrome ◽  
Brain Development ◽  
Chromosome 21 ◽  
Early Brain Development ◽  
The Central Nervous System ◽  
Circuit Development ◽  
And Function ◽  
The Impact ◽  
The Brain

Down Syndrome (DS) is the most common genetic cause of intellectual disability in which delays and impairments in brain development and function lead to neurological and cognitive phenotypes. Traditionally, a neurocentric approach, focusing on neurons and their connectivity, has been applied to understanding the mechanisms involved in DS brain pathophysiology with an emphasis on how triplication of chromosome 21 leads to alterations in neuronal survival and homeostasis, synaptogenesis, brain circuit development, and neurodegeneration. However, recent studies have drawn attention to the role of non-neuronal cells, especially astrocytes, in DS. Astrocytes comprise a large proportion of cells in the central nervous system (CNS) and are critical for brain development, homeostasis, and function. As triplication of chromosome 21 occurs in all cells in DS (with the exception of mosaic DS), a deeper understanding of the impact of trisomy 21 on astrocytes in DS pathophysiology is warranted and will likely be necessary for determining how specific brain alterations and neurological phenotypes emerge and progress in DS. Here, we review the current understanding of the role of astrocytes in DS, and discuss how specific perturbations in this cell type can impact the brain across the lifespan from early brain development to adult stages. Finally, we highlight how targeting, modifying, and/or correcting specific molecular pathways and properties of astrocytes in DS may provide an effective therapeutic direction given the important role of astrocytes in regulating brain development and function.

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