Abstract
We have shown previously, that mice lacking tumor necrosis factor-α(TNF-α) receptor 1 (TNFR1) exhibit greater hippocampal neurodegeneration, suggesting that TNFR1 may be protective in kainic acid (KA)-induced neurotoxicity. Here, we aim to clarify the role of TNF-α in neurodegenerative disorders and to elucidate its potential signaling pathways. TNF-αknockout (KO) mice and wild-type (WT) mice were treated with KA intranasally and, seizure severity measures obtained, Behavioral tests, including Elevated Plus-Maze™, open-field, Y-maze were also performed. Five days following KA treatment, immunohistochemical methods were used to assess neuronal degeneration and glial activation. The production of nitric oxide (NO) and the expression of nuclear factor kappaB (NF-κB) and AKT in the hippocampus were also measured. Compared with WT mice, TNF-α KO mice were more susceptibile to KA-induced neurotoxicity, as demonstrated by more severe seizures, measurable behavior changes, greater neuronal degeneration in hippocampus, elevated glial activation and NO production. Additionally, KA-treatment up-regulated the expression of NFκB in TNF-α KO mice to a greater degree than in KA-treated WT mice. We conclude that TNF-αdeficiency adversely influences KAinduced neurotoxicity and that TNF-αmay play a protective role in KA-induced neurotoxicity via the down-regulation of NFκB signaling pathway.
Keywords: TNF-α, kainic acid, neurotoxicity, hippocampus, NFκB.
Current Alzheimer Research
Title:Possible Protecting Role of TNF-α in Kainic Acid-induced Neurotoxicity Via Down-Regulation of NFκB Signaling Pathway
Volume: 10 Issue: 6
Author(s): Xing-Mei Zhang, Xiang-Yu Zheng, S. S. Sharkawi, Yang Ruan, Naheed Amir, Sheikh Azimullah, M. Y. Hasan, Jie Zhu and Abdu Adem
Affiliation:
Keywords: TNF-α, kainic acid, neurotoxicity, hippocampus, NFκB.
Abstract: We have shown previously, that mice lacking tumor necrosis factor-α(TNF-α) receptor 1 (TNFR1) exhibit greater hippocampal neurodegeneration, suggesting that TNFR1 may be protective in kainic acid (KA)-induced neurotoxicity. Here, we aim to clarify the role of TNF-α in neurodegenerative disorders and to elucidate its potential signaling pathways. TNF-αknockout (KO) mice and wild-type (WT) mice were treated with KA intranasally and, seizure severity measures obtained, Behavioral tests, including Elevated Plus-Maze™, open-field, Y-maze were also performed. Five days following KA treatment, immunohistochemical methods were used to assess neuronal degeneration and glial activation. The production of nitric oxide (NO) and the expression of nuclear factor kappaB (NF-κB) and AKT in the hippocampus were also measured. Compared with WT mice, TNF-α KO mice were more susceptibile to KA-induced neurotoxicity, as demonstrated by more severe seizures, measurable behavior changes, greater neuronal degeneration in hippocampus, elevated glial activation and NO production. Additionally, KA-treatment up-regulated the expression of NFκB in TNF-α KO mice to a greater degree than in KA-treated WT mice. We conclude that TNF-αdeficiency adversely influences KAinduced neurotoxicity and that TNF-αmay play a protective role in KA-induced neurotoxicity via the down-regulation of NFκB signaling pathway.
Export Options
About this article
Cite this article as:
Zhang Xing-Mei, Zheng Xiang-Yu, Sharkawi S. S., Ruan Yang, Amir Naheed, Azimullah Sheikh, Hasan Y. M., Zhu Jie and Adem Abdu, Possible Protecting Role of TNF-α in Kainic Acid-induced Neurotoxicity Via Down-Regulation of NFκB Signaling Pathway, Current Alzheimer Research 2013; 10 (6) . https://dx.doi.org/10.2174/15672050113109990007
DOI https://dx.doi.org/10.2174/15672050113109990007 |
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
-
Oxidative Stress in the Molecular Mechanism of Pathogenesis at Different Diseased States of Organism in Clinics and Experiment
Current Drug Targets - Inflammation & Allergy Use of Intravenous Immunoglobulin in the Treatment of Immune-Mediated Demyelinating Diseases of the Nervous System
Current Pharmaceutical Design Current Status of Epigenetics and Anticancer Drug Discovery
Anti-Cancer Agents in Medicinal Chemistry A Focus on Microfluidics and Nanotechnology Approaches for the Ultra Sensitive Detection of MicroRNA
MicroRNA The New Challenges of Brain PET Imaging Technology
Current Medical Imaging Glycogen Metabolism and Brain Pathologies
Central Nervous System Agents in Medicinal Chemistry Is Going for Cure in CML Targeting Aberrant Glycogen Synthase Kinase 3β?
Current Drug Targets Ion Channels as Medicinal Targets of Biological Toxins: The Impact of Automated Patch-Clamp Electrophysiology
Current Topics in Medicinal Chemistry Advances in the Physiology of GPR55 in the Central Nervous System
Current Neuropharmacology GABAA Receptor Specific Pyrazolopyrimidines as Potential Imaging Agents: In Vivo Characteristics of a New 18F-labelled Indiplon Derivative
Current Radiopharmaceuticals Evaluation of Specific Antibody Responses in Patients with Selective IgA Deficiency and Ataxia Telangiectasia
Endocrine, Metabolic & Immune Disorders - Drug Targets Drug Targets of Migraine and Neuropathy: Treatment of Hyperexcitability
CNS & Neurological Disorders - Drug Targets Neurological Disorders in Mice Lacking Glycogenes that are Mainly Expressed in Brain
CNS & Neurological Disorders - Drug Targets Adeno-Associated Virus Vectors: Immunobiology and Potential Use for Immune Modulation
Current Gene Therapy Scientific Prediction and Prophetic Patenting in Drug Discovery
Recent Patents on CNS Drug Discovery (Discontinued) Regulators of Platelet cAMP Levels: Clinical and Therapeutic Implications
Current Medicinal Chemistry Targeting Pain-evoking Transient Receptor Potential Channels for the Treatment of Pain
Current Neuropharmacology An Update on Peptide Drugs for Voltage-Gated Calcium Channels
Recent Patents on CNS Drug Discovery (Discontinued) A Compendium of Volatile Organic Compounds (VOCs) Released By Human Cell Lines
Current Medicinal Chemistry Ameliorative Potential of Glycyrrhiza glabra Extracts on Memory Impairments in Stress Triggered Rats
Current Traditional Medicine