Abstract
Neuroinflammation has emerged as an important cause of cognitive decline during aging and in Alzheimer’s disease (AD). Chronic low-grade inflammation is observed in obesity and diabetes, which are important risk factors for AD. Therefore, we examined the markers of inflammation in the brain hippocampal samples of Zucker diabetic fatty (ZDF) rats. Pathway-specific gene expression profiling revealed significant increases in the expression of oxidative stress and inflammatory genes. Western blot analysis further showed the activation of NF-kB, defective CREB phosphorylation, and decreases in the levels of neuroprotective CREB target proteins, including Bcl-2, BDNF, and BIRC3 in the diabetic rat brain samples, all of which are related to AD pathology. As therapies based on glucagon-like peptide-1 (GLP-1) are effective in controlling blood glucose levels in type 2 diabetic patients, we tested the in vivo actions of GLP-1 in the diabetic brain by a 10-wk treatment of ZDF rats with alogliptin, an inhibitor of dipeptidyl peptidase. Alogliptin increased the circulating levels of GLP-1 by 125% and decreased blood glucose in diabetic rats by 59%. Normalization of defective signaling to CREB in the hippocampal samples of treated diabetic rats resulted in the increased expression of CREB targets. Dual actions of GLP-1 in the pancreatic beta cells and in the brain suggest that incretin therapies may reduce cognitive decline in the aging diabetic patients and also have the potential to be used in treating Alzheimer’s patients.
Keywords: Brain, cognitive function and Alzheimer’s disease, CREB, Diabetes, dipeptidyl peptidase-4, Glucagon-like peptide- 1, hippocampus, inflammation, insulin, oxidative stress.
Current Alzheimer Research
Title:Glucagon-Like Peptide-1-Mediated Modulation of Inflammatory Pathways in the Diabetic Brain: Relevance to Alzheimer’s Disease
Volume: 13 Issue: 12
Author(s): LiMei Qin, Thomas Chong, Richard Rodriguez and Subbiah Pugazhenthi
Affiliation:
Keywords: Brain, cognitive function and Alzheimer’s disease, CREB, Diabetes, dipeptidyl peptidase-4, Glucagon-like peptide- 1, hippocampus, inflammation, insulin, oxidative stress.
Abstract: Neuroinflammation has emerged as an important cause of cognitive decline during aging and in Alzheimer’s disease (AD). Chronic low-grade inflammation is observed in obesity and diabetes, which are important risk factors for AD. Therefore, we examined the markers of inflammation in the brain hippocampal samples of Zucker diabetic fatty (ZDF) rats. Pathway-specific gene expression profiling revealed significant increases in the expression of oxidative stress and inflammatory genes. Western blot analysis further showed the activation of NF-kB, defective CREB phosphorylation, and decreases in the levels of neuroprotective CREB target proteins, including Bcl-2, BDNF, and BIRC3 in the diabetic rat brain samples, all of which are related to AD pathology. As therapies based on glucagon-like peptide-1 (GLP-1) are effective in controlling blood glucose levels in type 2 diabetic patients, we tested the in vivo actions of GLP-1 in the diabetic brain by a 10-wk treatment of ZDF rats with alogliptin, an inhibitor of dipeptidyl peptidase. Alogliptin increased the circulating levels of GLP-1 by 125% and decreased blood glucose in diabetic rats by 59%. Normalization of defective signaling to CREB in the hippocampal samples of treated diabetic rats resulted in the increased expression of CREB targets. Dual actions of GLP-1 in the pancreatic beta cells and in the brain suggest that incretin therapies may reduce cognitive decline in the aging diabetic patients and also have the potential to be used in treating Alzheimer’s patients.
Export Options
About this article
Cite this article as:
Qin LiMei, Chong Thomas, Rodriguez Richard and Pugazhenthi Subbiah, Glucagon-Like Peptide-1-Mediated Modulation of Inflammatory Pathways in the Diabetic Brain: Relevance to Alzheimer’s Disease, Current Alzheimer Research 2016; 13 (12) . https://dx.doi.org/10.2174/1567205013666160401114751
DOI https://dx.doi.org/10.2174/1567205013666160401114751 |
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
-
Clinical Applications of Positron Emission Tomography (PET) Imaging in Medicine: Oncology, Brain Diseases and Cardiology
Current Radiopharmaceuticals CD95 Signaling in Cancer Treatment
Current Pharmaceutical Design Traversing the Skin Barrier with Nano-emulsions
Current Drug Delivery Lipoprotein(a): Current Perspectives
Current Vascular Pharmacology The Use of Anthracyclines for Therapy of CNS Tumors
Anti-Cancer Agents in Medicinal Chemistry The Potential of Trace Amines and Their Receptors for Treating Neurological and Psychiatric Diseases
Reviews on Recent Clinical Trials Role of miR-193a in Cancer: Complexity and Factors Control the Pattern of its Expression
Current Cancer Drug Targets Hyperprolactinemia Secondary to Pituitary Microadenoma Versus Haloperidol- A Diagnostic Enigma. A Case Report and Brief Review
Current Drug Safety Aptamers Against Cell Surface Receptors: Selection, Modification and Application
Current Medicinal Chemistry Multiligand Endocytosis and Congenital Defects: Roles of Cubilin, Megalin and Amnionless
Current Pharmaceutical Design Resistance to Anti-VEGF Agents
Current Pharmaceutical Design The Interaction of Histone Deacetylase Inhibitors and DNA Methyltransferase Inhibitors in the Treatment of Human Cancer Cells
Current Medicinal Chemistry - Anti-Cancer Agents Biotransformation of Endocrine Disrupting Compounds by Selected Phase I and Phase II Enzymes – Formation of Estrogenic and Chemically Reactive Metabolites by Cytochromes P450 and Sulfotransferases
Current Medicinal Chemistry Patents on Technologies of Human Tissue and Organ Regeneration from Pluripotent Human Embryonic Stem Cells
Recent Patents on Regenerative Medicine Target-based Anti-angiogenic Therapy in Breast Cancer
Current Pharmaceutical Design Recent Advances in Antiviral Agents: Established and Innovative Therapies for Viral Hepatitis
Mini-Reviews in Medicinal Chemistry Meet Our Editor-in-Chief
Clinical Cancer Drugs Malignant Mesothelioma: Biology, Diagnosis and Therapeutic Approaches
Current Molecular Pharmacology Role of Nuclear Steroid Receptors in Apoptosis
Current Medicinal Chemistry Imatinib Mesylate for the Treatment of Solid Tumours: Recent Trials and Future Directions
Current Enzyme Inhibition