title: Development of a Novel and Robust Pharmacological Model of Okadaic Acid-induced Alzheimer's Disease in Zebrafish.
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.
authors: Shadia E
authors: SE
authors: Nada
authors: Frederick E
authors: FE
authors: Williams
authors: Department of Medicinal and Biological Chemistry, University of Toledo, 3000 Arlington Avenue, Toledo, Ohio, 43614. zahoor.shah@utoledo.edu.
authors: Zahoor A
authors: ZA
authors: Shah
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D019319:Okadaic Acid / Q000633:toxicity*; D015027:Zebrafish / Q000378:metabolism
chemical_list: D019319:Okadaic Acid