Abstract
Alzheimer’s disease (AD) is the leading neurodegenerative disorder affecting the world’s elderly population. Most experimental models of AD are transgenic or pharmacological in nature, and do not simulate the entire pathophysiology. In the present study, we developed a pharmacologically induced AD using the zebrafish, a species that can recapitulate most of the phenotypes of the disease. The pharmacological agent being used, okadaic acid (OKA) has also been utilized to study AD in other species. In this model, the immunohistochemistry of phosphorylated glycogen synthase-3α/β, Aβ, p-tau, tau protein, and senile plaque formation in zebrafish brain were all significantly increased with increasing exposure to OKA. These represent the majority of the histological hallmarks of AD pathophysiology. The observed changes were also accompanied by learning and memory deficits which are also important components in AD pathophysiology. Zebrafish disease models are gaining popularity mostly due to their economic cost and relevance to human disease pathophysiology. Current pharmacological methods of inducing AD in zebrafish are not adequately developed and do not represent all the features of the disease. OKA-induced AD in zebrafish can become a cost efficient model to study drug discovery for AD. It may also be used to unravel the molecular mechanisms underlying the complex pathophysiology that leads to AD using relatively economical species.
Keywords: Okadaic acid, Alzheimer’s Disease, Zebrafish, Tau & phospho-Tau protein, Amyloid β, glycogen synthase-3α/β &, phospho-GSK-3α/β, senile plaque.
CNS & Neurological Disorders - Drug Targets
Title:Development of a Novel and Robust Pharmacological Model of Okadaic Acid-induced Alzheimer’s Disease in Zebrafish
Volume: 15 Issue: 1
Author(s): Shadia E. Nada, Frederick E. Williams and Zahoor A. Shah
Affiliation:
Keywords: Okadaic acid, Alzheimer’s Disease, Zebrafish, Tau & phospho-Tau protein, Amyloid β, glycogen synthase-3α/β &, phospho-GSK-3α/β, senile plaque.
Abstract: Alzheimer’s disease (AD) is the leading neurodegenerative disorder affecting the world’s elderly population. Most experimental models of AD are transgenic or pharmacological in nature, and do not simulate the entire pathophysiology. In the present study, we developed a pharmacologically induced AD using the zebrafish, a species that can recapitulate most of the phenotypes of the disease. The pharmacological agent being used, okadaic acid (OKA) has also been utilized to study AD in other species. In this model, the immunohistochemistry of phosphorylated glycogen synthase-3α/β, Aβ, p-tau, tau protein, and senile plaque formation in zebrafish brain were all significantly increased with increasing exposure to OKA. These represent the majority of the histological hallmarks of AD pathophysiology. The observed changes were also accompanied by learning and memory deficits which are also important components in AD pathophysiology. Zebrafish disease models are gaining popularity mostly due to their economic cost and relevance to human disease pathophysiology. Current pharmacological methods of inducing AD in zebrafish are not adequately developed and do not represent all the features of the disease. OKA-induced AD in zebrafish can become a cost efficient model to study drug discovery for AD. It may also be used to unravel the molecular mechanisms underlying the complex pathophysiology that leads to AD using relatively economical species.
Export Options
About this article
Cite this article as:
Nada E. Shadia, Williams E. Frederick and Shah A. Zahoor, Development of a Novel and Robust Pharmacological Model of Okadaic Acid-induced Alzheimer’s Disease in Zebrafish, CNS & Neurological Disorders - Drug Targets 2016; 15 (1) . https://dx.doi.org/10.2174/1871527314666150821105602
DOI https://dx.doi.org/10.2174/1871527314666150821105602 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...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
Related Articles
-
Effect of Fenofibrate on the Concentration and Relative Distribution of LDL Subfractions in Patients with Combined Dyslipidemia
Letters in Drug Design & Discovery Integrins: Novel Therapeutic Targets for Cardiovascular Diseases
Cardiovascular & Hematological Agents in Medicinal Chemistry Irbesartan and Hydrochlorothiazide Association in the Treatment of Hypertension
Current Vascular Pharmacology MicroRNA Regulatory Network in Human Colorectal Cancer
Mini-Reviews in Medicinal Chemistry The Risk of Adverse Drug Reactions in Older Patients: Beyond Drug Metabolism
Current Drug Metabolism Incretin-Based Antidiabetic Agents for the Management of Non-Alcoholic Fatty Liver Disease
Current Vascular Pharmacology Anti-Hyperglycemic and Hypolipidemic Effects of Different Aloe vera (Aloe Barbadensis Miller) Extracts in the Management of Obesity and Diabetes
Current Nutrition & Food Science Editorial (Thematic Issue: Disease Control and Active and Healthy Ageing: New Paradigms of Therapeutic Strategy)
Current Pharmaceutical Design The Role of Catecholamines in Formation and Resolution of Pulmonary Oedema
Cardiovascular & Hematological Disorders-Drug Targets Myocardial Contrast Echocardiography: Role in Clinical Cardiology
Current Vascular Pharmacology Bioprocess and Bioreactor: Next Generation Technology for Production of Potential Plant-based Antidiabetic and Antioxidant Molecules
Current Medicinal Chemistry Influences of Maternal Nutritional Status on Vascular Function in the Offspring
Current Drug Targets Design and Development of Nanovehicle-Based Delivery Systems for Preventive or Therapeutic Supplementation with Flavonoids
Current Medicinal Chemistry Bariatric Surgery - Effects on Obesity and Related co-Morbidities
Current Diabetes Reviews Editorial [ Hot Topic: Antidepressant Drug Design (Executive Editor: Lee E. Schechter)]
Current Pharmaceutical Design The Role of Oxidative Stress in Smoking-Related Diseases
Mini-Reviews in Organic Chemistry Biomarkers Associated with Vulnerable Atheromatous Plaque
Current Medicinal Chemistry Inflammatory Cytokines, Growth Factors, and Depression
Current Pharmaceutical Design The Mechanism of Calcitriol in Cancer Prevention and Treatment
Current Medicinal Chemistry Breast Cancer Chemoprevention: Current Perspectives
Current Enzyme Inhibition