scholarly journals MiR-384 Regulates Reelin by Inhibiting ADAMTS4 in Neuronal Cell Lines

2021 ◽  
Author(s):  
Qiushi Cao ◽  
Bisheng Huang ◽  
Ping Wang ◽  
Gang Zhao ◽  
Min Zhao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Cell Lines ◽  
Western Blotting ◽  
Neuronal Cell ◽  
Luciferase Reporter ◽  
Control Group ◽  
Vitro Assay ◽  
Neuronal Cell Lines

MicroRNAs (miRNAs) are important regulators of gene expression at the post-transcriptional level. The present study aims to investigate the role of miR-384 in Reelin by regulating ADAMTS4 in neuronal cell lines. Brain tissues from Aβ1-42 induced mouse model of Alzheimer's disease and the control group were collected. RT-PCR, Western blotting and immunohistochemistry were performed to detect the levels of ADAMTS4 and miR-384 in tissues. Luciferase reporter assay, Western blotting and in vitro assay were used to validate that ADAMTS4 was the target gene of miR-384. Neuronal cell line, Neuro-2a, was selected for transfection assay. ADAMTS4 was significantly down-regulated in hippocampi of Alzheimer's disease mouse model, and negatively correlated with miR-384. Then, ADAMTS4 was identified as a direct target of miR-384. Over-expressing of miR-384 in Neuro-2a showed that ADAMTS4 and the cleaved Reelin fragments were down regulated, and proliferation of neuronal cell lines (Neuro-2a and SH-SY5Y) were inhibited through DAB-1 pathway. In conclusion, these results revealed that miR-384 may play a regulatory role in Reelin via inhibiting ADAMTS4 in neuronal cell lines.

Properties of neurotoxic peptides related to the BRI gene

2002 ◽  
Vol 30 (4) ◽  
pp. 557-559 ◽  
Author(s):  
B. Austen ◽  
O. EI-Agnaf ◽  
S. Nagala ◽  
B. Patel ◽  
N. Gunasekera ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mass ◽  
Cell Lines ◽  
Clinical Symptoms ◽  
Neuronal Cell ◽  
Reduced Form ◽  
Straight Chain ◽  
Human Neuronal Cell ◽  
Neuronal Cell Lines

Mutations in the BRI gene are thought to cause dementias in members of families. The clinical symptoms are similar to those of Alzheimer's disease, but with additional ocular and hearing deficits, and spasticity. The mutations lead to the release of the 34-residue peptides, ABri and ADan, in the brains of afflicted individuals. We have synthesized the peptides in their straight-chain and oxidized cyclic forms and shown that the oxidized form of ABri and reduced form of ADan are toxic to human neuronal cell lines in culture. Neurotoxicity correlates with the extent of formation of SDS-stable non-fibrillar low-molecular-mass oligomers (SSNFOs).

scholarly journals Lipid Peroxidation in Chronic Cerebral HypoperfusionInduced Neurodegeneration in Rats

2020 ◽  
Vol 10 (2) ◽  
Author(s):  
Anil Kumar S ◽  
Saif SA ◽  
Oothuman P ◽  
Mustafa MIA
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipid Peroxidation ◽  
Neurodegenerative Disorders ◽  
Neuronal Damage ◽  
Neuronal Cell ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Control Group ◽  
Vessel Occlusion

Introduction: Reduced cerebral blood fl ow is associated with neurodegenerative disorders and dementia, in particular. Experimental evidence has demonstrated the initiating role of chronic cerebral hypoperfusion in neuronal damage to the hippocampus, the cerebral cortex, the white matter areas and the visual system. Permanent, bilateral occlusion of the common carotid arteries of rats (two vessel occlusion - 2VO) has been introduced for the reproduction of chronic cerebral hypoperfusion as it occurs in Alzheimer’s disease and human aging. Increased generation of free radicals through lipid peroxidation can damage neuronal cell membrane. Markers of lipid peroxidation have been found to be elevated in brain tissues and body fl uids in neurodegenerative diseases, including Alzheimer’s disease, Parkinson disease and amyotrophic lateral sclerosis. Materials and Methods: Malondialdehyde (MDA), final product of lipid peroxidation, was estimated by thiobarbituric acid-reactive substances (TBARS) assay kit at eight weeks after induction of 2VO in the rats and control group. Results: Our study revealed a highly signifi cant (p<0.001) increase in the mean MDA concentration (12.296 ± 1.113 μM) in 2VO rats as compared to the control group (5.286 ± 0.363 μM) rats. Conclusion: Therapeutic strategies to modulate lipid peroxidation early throughout the course of the disease may be promising in slowing or possibly preventing neurodegenerative disorders.

scholarly journals A Dietary Ketone Ester Normalizes Abnormal Behavior in a Mouse Model of Alzheimer’s Disease

2020 ◽  
Vol 21 (3) ◽  
pp. 1044
Author(s):  
Robert J. Pawlosky ◽  
Yoshihero Kashiwaya ◽  
M. Todd King ◽  
Richard L. Veech
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Tca Cycle ◽  
Abnormal Behavior ◽  
Control Group ◽  
Brain Glucose ◽  
Model Of Alzheimer’S Disease ◽  
Brain Glucose Utilization ◽  
Ketone Ester

Because of a decreased sensitivity toward insulin, a key regulator of pyruvate dehydrogenase (PDH), Alzheimer’s patients have lower brain glucose utilization with reductions in Tricarboxylic Acid (TCA) cycle metabolites such as citrate, a precursor to n-acetyl-aspartate. In the 3xTgAd mouse model of Alzheimer’s disease (AD), aging mice also demonstrate low brain glucose metabolism. Ketone metabolism can overcome PDH inhibition and restore TCA cycle metabolites, thereby enhancing amino acid biosynthesis. A ketone ester of d-β-hydroxybutyrate was incorporated into a diet (Ket) and fed to 3xTgAd mice. A control group was fed a calorically matched diet (Cho). At 15 months of age, the exploratory and avoidance-related behavior patterns of the mice were evaluated. At 16.5 months of age, the animals were euthanized, and their hippocampi were analyzed for citrate, α-ketoglutarate, and amino acids. In the hippocampi of the Ket-fed mice, there were higher concentrations of citrate and α-ketoglutarate as well as higher concentrations of glutamate, aspartate and n-acetyl-aspartate compared with controls. There were positive associations between (1) concentrations of aspartate and n-acetyl-aspartate (n = 14, R = 0.9327), and (2) α-ketoglutarate and glutamate (n = 14, R = 0.8521) in animals maintained on either diet. Hippocampal n-acetyl-aspartate predicted the outcome of several exploratory and avoidance-related behaviors. Ketosis restored citrate and α-ketoglutarate in the hippocampi of aging mice. Higher concentrations of n-acetyl-aspartate corresponded with greater exploratory activity and reduced avoidance-related behavior.

scholarly journals Meox2 haploinsufficiency increases neuronal cell loss in a mouse model of Alzheimer's disease

2016 ◽  
Vol 42 ◽  
pp. 50-60 ◽  
Author(s):  
Ileana Soto ◽  
Weronika A. Grabowska ◽  
Kristen D. Onos ◽  
Leah C. Graham ◽  
Harriet M. Jackson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Neuronal Cell ◽  
Cell Loss ◽  
Model Of Alzheimer’S Disease ◽  
Neuronal Cell Loss

scholarly journals Platelet Tau Protein as a Potential Peripheral Biomarker in Alzheimer’s Disease: An Explorative Study

2018 ◽  
Vol 15 (9) ◽  
pp. 800-808 ◽  
Author(s):  
Elizabeta B. Mukaetova-Ladinska ◽  
Zeinab Abdell-All ◽  
Joana Andrade ◽  
Joaquim Alves da Silva ◽  
Irina Boksha ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Blood Platelets ◽  
Neuronal Cell ◽  
Clinical Settings ◽  
Neuronal Cell Lines ◽  
Specific Proteins ◽  
And Control ◽  
T Tau

Background: Cerebrospinal fluid (CSF) measures of tau and amyloid proteins have now been largely accepted to be a diagnostic tool to aid the clinical diagnosis of Alzheimer's disease (AD), but CSF is not routinely obtained in most clinical settings. There is a need, therefore, to uncover additional readily accessible peripheral biomarkers that will enable comprehensive detection of AD-specific proteins in blood and blood derivates. Objectives: Blood platelets contain proteins found in neuronal cell lines, including tau protein. Since tau protein is a characteristic of AD-neuropathology, platelet tau protein may be closely related to the central nervous process occurring in neurodegeneration. Method: Platelets from 25 AD and 26 control subjects were analysed for the microtubule-binding and C-terminal region, as well as two tau phosphorylation sites (Ser202/Thr205 and Thr181). Results: Tau protein measures did not discriminate between AD and control individuals. However, subjects with MMSE 24-27 had elevated C-terminal end tau protein (p=0.049) compared to those with MMSE >27, whereas older AD subjects (>80 years) showed higher t-tau protein in comparison to younger AD (<80 years; p=0.009) and control (<80 years; p=0.011) participants. Conclusions: These initial findings not only confirm that platelet tau protein can be measured, but also indicate that platelet tau measures merit further study as they may be useful in indicating early stages of cognitive impairment. Further studies on larger number of participants are needed to confirm our findings.

scholarly journals Faradarmani Consciousness Field Suppresses Alzheimer’s Disease Development in Both in Vitro and in Vivo Models of The Disease

2021 ◽  
Author(s):  
Mohammad Ali Taheri ◽  
Sara Torabi ◽  
Noushin Nabavi ◽  
Farid Semsarha
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Tau Protein ◽  
Elevated Plus Maze ◽  
Neuronal Cell ◽  
Neural Cell ◽  
Microtubule Assembly ◽  
In Vivo Models ◽  
Plus Maze

Abstract Background: Alzheimer’s Disease (AD) is one of the most common causes of dementia, imposing large financial and psychological burdens on nations worldwide. Thus, we are in dire need for new treatment strategies or drugs for this disease. The aim of this study is to investigate the effects of a novel non-pharmacological method in the treatment of Alzheimer’s disease, based on Taheri's Consciousness Field approach. This approach works at the level of cellular and molecular processes and is tested in neuronal cells of AD mouse models. Methods: In this study, we established a neuron cell culture from an AD mouse model as well as a traumatic brain injury mouse model. We then measured changes in amyloidopathy, tau protein content, microtubule assembly, neuronal cell survival, and finally behavior of TBI mice in elevated Plus Maze under treatment of the Faradarmani Consciousness Field (FCF). Results: According to the results of this study, treatment of neural cell and mouse model of Alzheimer's disease by the FCF, leads to about complete survival of neural cell models and elimination of amyloidopathy and tau protein and remarkable behavioral improvement of the treated TBI mice model in the elevated plus maze. Conclusions: Based on the results, the FCF treatment suppresses AD development in the laboratory models. In this regard, conducting a human clinical study with the aim of introducing a new global complementary and alternative medicine in AD treatment is highly recommended.

scholarly journals Brain Dicer1 is down-regulated in a mouse model of Alzheimer’s disease via Aβ42-induced repression of nuclear factor erythroid 2-related factor 2

2020 ◽  
Author(s):  
Yan Wang ◽  
Meiling Lian ◽  
Jing Zhou ◽  
shengzhou wu
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Luciferase Reporter ◽  
Cultured Neurons ◽  
Related Factor ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Dicer1 Expression

Abstract Background Oxidative stress critically underlies the neurodegenerative pathogenesis of Alzheimer's disease (AD). Depletion of Dicer1, an endoribonuclease central to microRNA maturation, also leads to neurodegeneration. We therefore hypothesized that altered Dicer1 expression may play a role in AD. Results Using immunoblotting and quantitative real-time PCR, we found that Dicer1 protein and mRNA levels were reduced in the hippocampi of animals of the AD mouse model APPswe/PSEN1dE9 compared with littermate controls. SiRNA-meditated Dicer1 knockdown induced oxidative stress, reduced mitochondrial intermembrane potential, and increased apoptosis in cultured neurons. Aβ42 exposure decreased Dicer1 and also down-regulated the oxidative stress–induced transcriptional regulator nuclear factor erythroid 2-related factor 2 (Nrf2). Conversely, Nrf2 overexpression increased Dicer1 mRNA and protein levels and reverted the Aβ42-induced Dicer1 reduction. To further investigate Dicer1 regulation, we cloned Dicer1 promoter variants harboring the Nrf2-binding site, the antioxidant response elements (ARE), into a luciferase reporter and found that simultaneous transfection of Nrf2-expressing plasmid increased luciferase expression from these promoter constructs. ChIP assays indicated that Nrf2 directly interacted with the ARE motifs in the Dicer1 promoter. Furthermore, Dicer1 overexpression in cultured neurons reverted Aβ42-induced neurite deficits. Of note, injection of Dicer1-expressing adenovirus into the hippocampus of the AD mice significantly improved spatial learning. Conclusions These findings indicate that Dicer1 expression is reduced in the AD brain and that chronic Aβ exposure decreases Dicer1 levels in neurons via Nrf2–ARE signaling. Our results uncover a significant role for Dicer1 in AD and highlight that Dicer1 expression responds to oxidative stress in the brain.

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