Development of a Novel and Robust Pharmacological Model of Okadaic Acid-induced Alzheimer’s Disease in Zebrafish

Author(s): Shadia E. Nada , Frederick E. Williams , Zahoor A. Shah .

Journal Name: CNS & Neurological Disorders - Drug Targets

Volume 15 , Issue 1 , 2016

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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.

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Article Details

VOLUME: 15
ISSUE: 1
Year: 2016
Page: [86 - 94]
Pages: 9
DOI: 10.2174/1871527314666150821105602

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