scholarly journals IKK2/NF-κB Activation in Astrocytes Reduces Amyloid β Deposition: A Process Associated with Specific Microglia Polarization

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2669
Author(s):  
Shu Yang ◽  
Alexander Magnutzki ◽  
Najwa Ouali Alami ◽  
Michael Lattke ◽  
Tabea Melissa Hein ◽  
...  
Keyword(s):  
Marker Gene ◽  
Amyloid Β ◽  
Specific Marker ◽  
App Processing ◽  
Beneficial Effects ◽  
Gene Profiles ◽  
Microglia Polarization ◽  
App23 Mouse ◽  
Plaque Clearance ◽  
The Impact

Alzheimer’s disease (AD) is a common neurodegenerative disease that is accompanied by pronounced neuroinflammatory responses mainly characterized by marked microgliosis and astrogliosis. However, it remains open as to how different aspects of astrocytic and microglial activation affect disease progression. Previously, we found that microglia expansion in the spinal cord, initiated by IKK2/NF-κB activation in astrocytes, exhibits stage-dependent beneficial effects on the progression of amyotrophic lateral sclerosis. Here, we investigated the impact of NF-κB-initiated neuroinflammation on AD pathogenesis using the APP23 mouse model of AD in combination with conditional activation of IKK2/NF-κB signaling in astrocytes. We show that NF-κB activation in astrocytes triggers a distinct neuroinflammatory response characterized by striking astrogliosis as well as prominent microglial reactivity. Immunohistochemistry and Congo red staining revealed an overall reduction in the size and number of amyloid plaques in the cerebral cortex and hippocampus. Interestingly, isolated primary astrocytes and microglia cells exhibit specific marker gene profiles which, in the case of microglia, point to an enhanced plaque clearance capacity. In contrast, direct IKK2/NF-κB activation in microglia results in a pro-inflammatory polarization program. Our findings suggest that IKK2/NF-κB signaling in astrocytes may activate paracrine mechanisms acting on microglia function but also on APP processing in neurons.

scholarly journals Shotgun lipidomics of liver and brain tissue of Alzheimer’s disease model mice treated with acitretin

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna A. Lauer ◽  
Daniel Janitschke ◽  
Malena dos Santos Guilherme ◽  
Vu Thu Thuy Nguyen ◽  
Cornel M. Bachmann ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Amyloid Β ◽  
Lipid Homeostasis ◽  
Medical Surveillance ◽  
Shotgun Lipidomics ◽  
App Processing ◽  
Cognitive Improvement ◽  
The Impact

AbstractAlzheimer’s disease (AD) is a very frequent neurodegenerative disorder characterized by an accumulation of amyloid-β (Aβ). Acitretin, a retinoid-derivative and approved treatment for Psoriasis vulgaris, increases non-amyloidogenic Amyloid-Precursor-Protein-(APP)-processing, prevents Aβ-production and elicits cognitive improvement in AD mouse models. As an unintended side effect, acitretin could result in hyperlipidemia. Here, we analyzed the impact of acitretin on the lipidome in brain and liver tissue in the 5xFAD mouse-model. In line with literature, triglycerides were increased in liver accompanied by increased PCaa, plasmalogens and acyl-carnitines, whereas SM-species were decreased. In brain, these effects were partially enhanced or similar but also inverted. While for SM and plasmalogens similar effects were found, PCaa, TAG and acyl-carnitines showed an inverse effect in both tissues. Our findings emphasize, that potential pharmaceuticals to treat AD should be carefully monitored with respect to lipid-homeostasis because APP-processing itself modulates lipid-metabolism and medication might result in further and unexpected changes. Moreover, deducing effects of brain lipid-homeostasis from results obtained for other tissues should be considered cautiously. With respect to acitretin, the increase in brain plasmalogens might display a further positive probability in AD-treatment, while other results, such as decreased SM, indicate the need of medical surveillance for treated patients.

scholarly journals Gallic acid is a dual α/β-secretase modulator that reverses cognitive impairment and remediates pathology in Alzheimer mice

2020 ◽  
Vol 295 (48) ◽  
pp. 16251-16266 ◽  
Author(s):  
Takashi Mori ◽  
Naoki Koyama ◽  
Tomotaka Yokoo ◽  
Tatsuya Segawa ◽  
Masahiro Maeda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mouse Model ◽  
Gallic Acid ◽  
Therapeutic Potential ◽  
Amyloid Β ◽  
Brain Inflammation ◽  
Amyloid Β Protein ◽  
App Processing ◽  
Beneficial Effects ◽  
Therapeutic Benefits

Several plant-derived compounds have demonstrated efficacy in pre-clinical Alzheimer's disease (AD) rodent models. Each of these compounds share a gallic acid (GA) moiety, and initial assays on this isolated molecule indicated that it might be responsible for the therapeutic benefits observed. To test this hypothesis in a more physiologically relevant setting, we investigated the effect of GA in the mutant human amyloid β-protein precursor/presenilin 1 (APP/PS1) transgenic AD mouse model. Beginning at 12 months, we orally administered GA (20 mg/kg) or vehicle once daily for 6 months to APP/PS1 mice that have accelerated Alzheimer-like pathology. At 18 months of age, GA therapy reversed impaired learning and memory as compared with vehicle, and did not alter behavior in nontransgenic littermates. GA-treated APP/PS1 mice had mitigated cerebral amyloidosis, including brain parenchymal and cerebral vascular β-amyloid deposits, and decreased cerebral amyloid β-proteins. Beneficial effects co-occurred with reduced amyloidogenic and elevated nonamyloidogenic APP processing. Furthermore, brain inflammation, gliosis, and oxidative stress were alleviated. We show that GA simultaneously elevates α- and reduces β-secretase activity, inhibits neuroinflammation, and stabilizes brain oxidative stress in a pre-clinical mouse model of AD. We further demonstrate that GA increases abundance of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10, Adam10) proprotein convertase furin and activates ADAM10, directly inhibits β-site APP cleaving enzyme 1 (BACE1, Bace1) activity but does not alter Adam10 or Bace1 transcription. Thus, our data reveal novel post-translational mechanisms for GA. We suggest further examination of GA supplementation in humans will shed light on the exciting therapeutic potential of this molecule.

scholarly journals The impact of capsaicinoids on APP processing in Alzheimer’s disease in SH-SY5Y cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marcus O. W. Grimm ◽  
Tamara Blümel ◽  
Anna A. Lauer ◽  
Daniel Janitschke ◽  
Christoph Stahlmann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Insulin Degrading Enzyme ◽  
App Processing ◽  
Positive Effects ◽  
Aβ Degradation ◽  
The Impact

Abstract The vanilloid capsaicin is a widely consumed spice, known for its burning and “hot” sensation through activation of TRPV1 ion-channels, but also known to decrease oxidative stress, inflammation and influence tau-pathology. Beside these positive effects, little is known about its effects on amyloid-precursor-protein (APP) processing leading to amyloid-β (Aβ), the major component of senile plaques. Treatment of neuroblastoma cells with capsaicinoids (24 hours, 10 µM) resulted in enhanced Aβ-production and reduced Aβ-degradation, leading to increased Aβ-levels. In detailed analysis of the amyloidogenic-pathway, both BACE1 gene-expression as well as protein-levels were found to be elevated, leading to increased β-secretase-activity. Additionally, γ-secretase gene-expression as well as activity was enhanced, accompanied by a shift of presenilin from non-raft to raft membrane-domains where amyloidogenic processing takes place. Furthermore, impaired Aβ-degradation in presence of capsaicinoids is dependent on the insulin-degrading-enzyme, one of the major Aβ-degrading-enzymes. Regarding Aβ-homeostasis, no differences were found between the major capsaicinoids, capsaicin and dihydrocapsaicin, and a mixture of naturally derived capsaicinoids; effects on Ca2+-homeostasis were ruled out. Our results show that in respect to Alzheimer’s disease, besides the known positive effects of capsaicinoids, pro-amyloidogenic properties also exist, enhancing Aβ-levels, likely restricting the potential use of capsaicinoids as therapeutic substances in Alzheimer’s disease.

scholarly journals Spatial Maps of Hepatocellular Carcinoma Transcriptomes Highlight an Unexplored Landscape of Heterogeneity and a Novel Gene Signature for Survival

2021 ◽  
Author(s):  
Nan Zhao ◽  
Yanhui Zhang ◽  
Runfen Cheng ◽  
Danfang Zhang ◽  
Fan Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Drug Targets ◽  
Marker Gene ◽  
Risk Groups ◽  
Gene Signature ◽  
Low Risk ◽  
Marker Genes ◽  
Specific Marker ◽  
Gene Profiles

Abstract Background: Hepatocellular carcinoma (HCC) are often present with satellite nodules, rendering current curative treatments ineffective in many patients. The heterogeneity of HCC is a major challenge in personalized medicine. The emergence of spatial transcriptomics (ST) provides a powerful strategy for delineating the complex molecular landscapes of tumors. Methods: In this study, we investigated tissue-wide gene expression heterogeneity in tumor and adjacent nonneoplastic tissues using ST technology. We analyzed the transcriptomes of nearly 10820 tissue regions and identified main gene expression clusters and their specific marker genes (differentially expressed genes, DEGs) in patients. The DEGs were analyzed from two perspectives. First of all, we identified two distinct gene profiles associated with satellite nodules and conducted a more comprehensive analysis for both gene profiles. Their clinical relevance for human HCC was validated with KM Plotter. Secondly, we screened DEGs with TCGA database to divide the HCC cohort into high- and low-risk groups according to Cox analysis. HCC patients from the ICGC cohort were used for validation. Kaplan Meier analysis was used to compare the overall survival (OS) between high- and low-risk groups. Univariate and multivariate Cox analyses were applied to determine the independent predictors for OS. Results: Novel markers for the prediction of satellite nodules and a tumor clusters specific marker genes signature model(6 genes) for HCC prognosis was constructed, respectively. Conclusion: The establishment of marker gene profiles may be an important step towards an unbiased view of HCC and the 6-genes signature can be used for prognostic prediction in HCC. This analysis will help us to clarify one of the possible soucres of HCC heterogeneity, uncover pathogenic mechanisms and novel anti-tumor drug targets.

HBOT Application at Cases of Gingival Inflammation

2019 ◽  
Author(s):  
Ilma Robo
Keyword(s):  
Root Resorption ◽  
Periodontal Diseases ◽  
Therapeutic Effects ◽  
Clinical Effects ◽  
Gingival Inflammation ◽  
Beneficial Effects ◽  
New Therapeutic Approaches ◽  
Short Period ◽  
Mechanical Therapy ◽  
The Impact

The treatment of periodontal diseases, mainly of their origin, with the most common clinical manifestation in form of gingival inflammation, is manifold and powerful, including: mechanical therapy, antibiotic, antiseptic and various approaches to treatment, which are recommended to be used within a short period of time. New therapeutic approaches have been proven as alternative treatment to conventional therapy, or in combination with conventional therapies, to reduce the number of periodontopathic pathogens in gingival sulcus. HBOT has a detrimental effect on periodontal microorganisms, as well as beneficial effects on the healing of periodontal tissue, increasing oxygen pressure in gingival pockets. Our study is aimed at reviewing the current published literature on hyperbaric oxygen therapy and focuses on role of HBOT as a therapeutic measure for the individual with periodontal disease in general and for the impact on the recovery of gingival inflammation. HBOT and periodontal treatment together, reduce up to 99% of the gram-negative anaerobic load of subgingival flora. HBOT, significantly reduces subgingival anaerobic flora. Clinical effects in 2-year follow-up of treated patients are sensitive. Reduction of gingival hemorrhage indexes, depth of peritoneum, plaque index, occurs in cases of combination of HBOT and detraction. Reduced load persists up to 2 months after therapy. The significant increase in connective tissue removal starts at the end of 2nd week, to achieve the maximum in week 3-6 of application. HBOT used for re-implantation, stimulates the healing of periodontal membrane, pulp, prevents root resorption, healing of periodontal lining tissues. HBOT, significantly reduces the hemorrhage index with 1.2 value difference, 0.7mm probe depth, reduces gingival fluid by 2. HGH exposure is increased by gingival blood flow, with a difference of 2 in measured value. The therapeutic effects of HBOT in the value of the evaluation index can be saved up to 1-year post treatment.

Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

2018 ◽  
Vol 15 (6) ◽  
pp. 531-543 ◽  
Author(s):  
Dominik Szwajgier ◽  
Ewa Baranowska-Wojcik ◽  
Kamila Borowiec
Keyword(s):  
Phenolic Acids ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Amyloid Β Peptide ◽  
Beneficial Effects ◽  
Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

Relation between cognitive disorders and type of physical activity: Results of the FréLE cohort

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
C Dupré ◽  
N Barth ◽  
A El Moutawakkil ◽  
F Béland ◽  
F Roche ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cognitive Decline ◽  
Proportional Hazards ◽  
Cognitive Disorders ◽  
The Elderly ◽  
Cognitive Status ◽  
Global Test ◽  
Professional Activities ◽  
Beneficial Effects ◽  
The Impact

Abstract Background Few previous cohorts have studied the different type of physical activities and the degree of cognitive decline. The objective of this work was to analyze the leisure, domestic and professional activities with mild and moderate cognitive disorders in older people living in community. Methods The study used data from the longitudinal and observational study, FrèLE (FRagility: Longitudinal Study of Expressions). The collected data included: socio-demographic variables, lifestyle, and health status (frailty, comorbidities, cognitive status, depression). Cognitive decline was assessed by using: MMSE (Mini-Mental State Examination) and MoCA (Montreal Cognitive Assessment). MoCA was used with two cut-offs (26 and 17) so as to define mild and moderate cognitive disorders Physical activity was assessed by the PASE (Physical Activity Scale for the Elderly), structured in three sections: leisure, domestic and professional activities. Spline and proportional hazards regression models (Cox) were used to estimate the risk of cognitive disorders. Results At baseline, 1623 participants were included and the prevalence of cognitive disorders was 6.9% (MMSE) and 7.2% (MoCA), mild cognitive disorders was 71.3%. The mean age was 77 years, and 52% of the participants were women. After a 2 years long follow-up, we found 6.9% (MMSE) and 6% (MoCA) cognitive disorders on participants. Analyses showed that domestic activities were associated to cognitive decline (HR = 0.52 [0.28-0.94] for MMSE and HR = 0.48 [0.28-0.80] for MoCA). No association were found with leisure and professional activities, and no spline were significant with mild cognitive disorders. Conclusions Analysis showed a relationship between cognitive disorders and type of physical activity, thanks to the use of specific questionnaire of elderly and two global test of cognition. These findings will contribute to the debate on the beneficial effects of physical activity on cognition. Key messages This work allowed to compare two test of cognition and their link with physical activity. It contributes to the debate on the beneficial effects of physical activity on cognition. The work allowed us to see the effect of the different types of physical activity and the impact of the statistical method on the results.

scholarly journals Microstructure and Durability Performance of Mortars with Volcanic Powder from Calbuco Volcano (Chile) after 4 Hardening Years

Materials ◽  
2021 ◽  
Vol 14 (7) ◽  
pp. 1751
Author(s):  
Rosa María Tremiño ◽  
Teresa Real-Herraiz ◽  
Viviana Letelier ◽  
José Marcos Ortega
Keyword(s):  
Water Absorption ◽  
Thermal Analyses ◽  
Length Change ◽  
Cement Industry ◽  
Chloride Diffusion ◽  
Beneficial Effects ◽  
State Diffusion ◽  
Calbuco Volcano ◽  
Reference Specimens ◽  
The Impact

One of the most popular ways to lessen the impact of the cement industry on the environment consists of substituting clinker by additions. The service life required for real construction elements is generally long, so it would be interesting to obtain information about the effects of new additions after a hardening period of several years. Analyzed here are the effects of the incorporation of volcanic ashes, coming from Calbuco volcano’s last eruption (Chile), as clinker replacement, in the durability and pore structure of mortars, after approximately 4 hardening years (1500 days), in comparison with reference specimens without additions. The substitution percentages of clinker by volcanic powder studied were 10% and 20%. The microstructure was characterized with mercury intrusion porosimetry and impedance spectroscopy. In order to evaluate the pozzolanic activity of the volcanic powder after 1500 days, differential thermal analyses were performed. Water absorption after immersion, steady-state diffusion coefficient and length change were also studied. In accordance with the results obtained, the 10% and 20% substitution of clinker by volcanic powder from the Calbuco volcano showed beneficial effects in the mortars after 4 years, especially regarding the microstructure and chloride diffusion, without noticeable influence in their water absorption.

scholarly journals Reproduction and biomarker responses of Eisenia fetida after exposure to imidacloprid in biochar-amended soil

Biochar ◽  
2021 ◽  
Author(s):  
Ngitheni Winnie-Kate Nyoka ◽  
Ozekeke Ogbeide ◽  
Patricks Voua Otomo
Keyword(s):  
Eisenia Fetida ◽  
Field Studies ◽  
Application Rate ◽  
Land Application ◽  
Acetylcholinesterase Inhibition ◽  
Beneficial Effects ◽  
Pesticide Pollution ◽  
The One ◽  
The Impact ◽  
Amended Soil

AbstractTerrestrial and aquatic ecosystems are increasingly threatened by pesticide pollution resulting from extensive use of pesticides, and due to the lack of regulatory measures in the developing world, there is a need for affordable means to lessen environmental effects. This study aimed to investigate the impact of biochar amendment on the toxicity of imidacloprid to life-cycle parameters and biomarker responses of the earthworm Eisenia fetida. E. fetida was exposed to 10% biochar-amended and non-amended OECD artificial soils spiked with 0, 0.75, 1.5, 2.25 and 3 mg imidacloprid/kg for 28 days. An LC50 of 2.7 mg/kg was only computed in the non-amended soil but not in the biochar-amended soil due to insignificant mortality. The EC50 calculated in the non-amended soil (0.92 mg/kg) for reproduction (fertility) was lower than the one computed in the biochar amended (0.98 mg/kg), indicating a decrease in toxicity in the biochar-amended substrate. Significant weight loss was observed at the two highest imidacloprid treatments in the non-amended soil and only at the highest treatment in the biochar-amended substrate, further highlighting the beneficial effects of biochar. Catalase activity decreased significantly at the two highest concentrations of non-amended soil. Yet, in the amended soil, the activity remained high, especially in the highest concentration, where it was significantly higher than the controls. This indicated more severe oxidative stress in the absence of biochar. In all non-amended treatments, there was a significant acetylcholinesterase inhibition, while lower inhibition percentages were observed in the biochar-amended soil. In most endpoints, the addition of biochar alleviated the toxic effects of imidacloprid, which shows that biochar has the potential to be useful in soil remediation. However, there is still a need for field studies to identify the most effective application rate of biochar for land application.

scholarly journals Exogenous application of growth stimulators improves the condition of maize exposed to soil drought

2021 ◽  
Vol 43 (4) ◽  
Author(s):  
Agnieszka Ostrowska ◽  
Maciej T. Grzesiak ◽  
Tomasz Hura
Keyword(s):  
Plant Growth ◽  
Developmental Stages ◽  
Aminolevulinic Acid ◽  
Stem Elongation ◽  
Development Stage ◽  
Photochemical Activity ◽  
Soil Drought ◽  
Beneficial Effects ◽  
Induced Changes ◽  
The Impact

AbstractSoil drought is a major problem in plant cultivation. This is particularly true for thermophilic plants, such as maize, which grow in areas often affected by precipitation shortage. The problem may be alleviated using plant growth and development stimulators. Therefore, the aim of the study was to analyze the effects of 5-aminolevulinic acid (5-ALA), zearalenone (ZEN), triacontanol (TRIA) and silicon (Si) on water management and photosynthetic activity of maize under soil drought. The experiments covered three developmental stages: three leaves, stem elongation and heading. The impact of these substances applied during drought stress depended on the plant development stage. 5-ALA affected chlorophyll levels, gas exchange and photochemical activity of PSII. Similar effects were observed for ZEN, which additionally induced stem elongation and limited dehydration. Beneficial effects of TRIA were visible at the stage of three leaves and involved leaf hydration and plant growth. A silicon preparation applied at the same developmental stage triggered similar effects and additionally induced changes in chlorophyll levels. All the stimulators significantly affected transpiration intensity at the heading stage.

Sign in / Sign up

Export Citation Format

Share Document