Abstract
Background: Chronic neuroinflammation caused by activation of microglia and astrocytes in the brain contributes to neuronal loss and disease progression in Alzheimer’s disease (AD). Recent research has identified type 2 diabetes mellitus (T2DM) as a risk factor for AD. High blood glucose (hyperglycemia) and the phenomenon of insulin resistance are being considered as the major factors contributing to an increased risk of AD. However, the mechanisms involved in this interaction remain unclear.
Objective: High glucose has been shown to increase release of pro-inflammatory mediators from various immune cells, including microglia. Since astrocytes are the most abundant glial cell type in the brain, we investigated the effects of elevated glucose concentrations (5.5-30.5 mM) on selected functions of cultured human astrocytes in the presence of inflammatory stimuli. Method: Experiments were conducted using primary human astrocytes and U-118 MG astrocytoma cells. Results: High glucose (30.5 mM) increased mRNA expression of interleukin (IL)-6 and secretion of both IL-6 and IL-8 by astrocytes. This astrocytic inflammatory response to high glucose did not appear to be mediated by augmented p38 or p44/42 mitogen activated protein kinase (MAPK) signaling pathways. In addition, high glucose increased the susceptibility of undifferentiated human SH-SY5Y neuronal cells and retinoic-acid differentiated SH-SY5Y cells to injury by hydrogen peroxide (H2O2) and fibrillar amyloid beta-42 protein (Aβ42), respectively. Conclusion: Our data indicate that hyperglycemia in T2DM may be one of the factors contributing to the observed increased risk of AD by exacerbating astrocyte-mediated neuroinflammation and neuronal injury caused by disease-associated agents.Keywords: Glucose, astrocytes, neuroinflammation, Alzheimer's disease, type 2 diabetes mellitus, Aβ42, hyperglycemia.
Current Alzheimer Research
Title:High Glucose Enhances Neurotoxicity and Inflammatory Cytokine Secretion by Stimulated Human Astrocytes
Volume: 14 Issue: 7
Author(s): Manpreet Bahniwal, Jonathan P. Little and Andis Klegeris*
Affiliation:
- Department of Biology, University of British Columbia Okanagan Campus, 3187 University Way, Kelowna, BC,Canada
Keywords: Glucose, astrocytes, neuroinflammation, Alzheimer's disease, type 2 diabetes mellitus, Aβ42, hyperglycemia.
Abstract: Background: Chronic neuroinflammation caused by activation of microglia and astrocytes in the brain contributes to neuronal loss and disease progression in Alzheimer’s disease (AD). Recent research has identified type 2 diabetes mellitus (T2DM) as a risk factor for AD. High blood glucose (hyperglycemia) and the phenomenon of insulin resistance are being considered as the major factors contributing to an increased risk of AD. However, the mechanisms involved in this interaction remain unclear.
Objective: High glucose has been shown to increase release of pro-inflammatory mediators from various immune cells, including microglia. Since astrocytes are the most abundant glial cell type in the brain, we investigated the effects of elevated glucose concentrations (5.5-30.5 mM) on selected functions of cultured human astrocytes in the presence of inflammatory stimuli. Method: Experiments were conducted using primary human astrocytes and U-118 MG astrocytoma cells. Results: High glucose (30.5 mM) increased mRNA expression of interleukin (IL)-6 and secretion of both IL-6 and IL-8 by astrocytes. This astrocytic inflammatory response to high glucose did not appear to be mediated by augmented p38 or p44/42 mitogen activated protein kinase (MAPK) signaling pathways. In addition, high glucose increased the susceptibility of undifferentiated human SH-SY5Y neuronal cells and retinoic-acid differentiated SH-SY5Y cells to injury by hydrogen peroxide (H2O2) and fibrillar amyloid beta-42 protein (Aβ42), respectively. Conclusion: Our data indicate that hyperglycemia in T2DM may be one of the factors contributing to the observed increased risk of AD by exacerbating astrocyte-mediated neuroinflammation and neuronal injury caused by disease-associated agents.Export Options
About this article
Cite this article as:
Bahniwal Manpreet, Little P. Jonathan and Klegeris Andis*, High Glucose Enhances Neurotoxicity and Inflammatory Cytokine Secretion by Stimulated Human Astrocytes, Current Alzheimer Research 2017; 14 (7) . https://dx.doi.org/10.2174/1567205014666170117104053
DOI https://dx.doi.org/10.2174/1567205014666170117104053 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Reactive Oxygen Species, Redox Signaling and Neuroinflammation in Alzheimer's Disease: The NF-κB Connection
Current Topics in Medicinal Chemistry Methionine AminoPeptidase Type-2 Inhibitors Targeting Angiogenesis
Current Topics in Medicinal Chemistry HLA-G - From Fetal Tolerance to a Regulatory Molecule in Inflammatory Diseases
Current Immunology Reviews (Discontinued) Druggability of Mortalin for Cancer and Neuro-Degenerative Disorders
Current Pharmaceutical Design The mTOR/4E-BP1/eIF4E Signalling Pathway as a Source of Cancer Drug Targets
Current Medicinal Chemistry p-Trifluoroacetophenone Oxime Ester Derivatives: Synthesis, Antimicrobial and Cytotoxic Evaluation and Molecular Modeling Studies
Letters in Drug Design & Discovery Antipsychotics as Psychosis Drugs and Neuroprotective Promoters Evaluated by Chemical QSAR - in silico and in vivo Studies
Letters in Drug Design & Discovery Apoptosis: A Key in Neurodegenerative Disorders
Current Neurovascular Research The Interaction Between FAK, MYCN, p53 and Mdm2 in Neuroblastoma
Anti-Cancer Agents in Medicinal Chemistry Poly(ADP-Ribosylation): Beneficial Effects of Its Inhibition
Current Enzyme Inhibition Iron Chelators as Anti-Neoplastic Agents: Current Developments and Promise of the PIH Class of Chelators
Current Medicinal Chemistry An Integrative Systems Analysis of High-grade Glioma Cell Lines: TLRs, Wnt, BRCA1, Netrins, STXBP1 and MDH1 Provide Putative Molecular Targets for Therapeutic Intervention
Current Pharmacogenomics and Personalized Medicine Possible Physiopathological Effects of the Transglutaminase Activity on the Molecular Mechanisms Responsible for Human Neurodegenerative Diseases
Recent Patents on CNS Drug Discovery (Discontinued) Oxysterol Derivatives of Cholesterol in Neurodegenerative Disorders
Current Medicinal Chemistry Biomarkers in Amyotrophic Lateral Sclerosis: Is There A Neurovascular Pathway?
Current Neurovascular Research Synthesis, Structure-Activity Relationships and Biological Activity of New Isatin Derivatives as Tyrosinase Inhibitors
Current Topics in Medicinal Chemistry An Orally Bioavailable c-Met Kinase Inhibitor Potently Inhibits Brain Tumor Malignancy and Growth
Anti-Cancer Agents in Medicinal Chemistry Imaging of EGFR and EGFR Tyrosine Kinase Overexpression in Tumors by Nuclear Medicine Modalities
Current Pharmaceutical Design Acute Hypersensitivity Reactions to Chemotherapy Agents: An Overview
Inflammation & Allergy - Drug Targets (Discontinued) Editorial (Hot Topic: Innovative Approaches for the Management of Pediatric Malignancies)
Current Medicinal Chemistry