Utilizing zebrafish and okadaic acid to study Alzheimer’s disease

Abstract

Despite the many years of extensive research using rodent models to study Alzheimer’s disease (AD), no cure or disease halting drug exists. An increasing number of people are suffering from the disease and a therapeutic intervention is needed. Therefore, it is necessary to have complementary models to aid in the drug discovery. The zebrafish animal model is emerging as a valuable model for the investigation of AD and neurodegenerative drug discovery. The main genes involved in human AD have homologous counterparts in zebrafish and have conserved function. The basic brain structure of the zebrafish is also conserved when compared to the mammalian brain. Recently an AD model was established by administering okadaic acid to zebrafish. It was used to test the efficacy of a novel drug, lanthionine ketimine-5-ethyl ester, and to elucidate its mechanism of action. This demonstrated the ability of the okadaic acid-induced AD zebrafish model to be implemented in the drug discovery process for therapeutics against AD.

Zebrafish as an Animal Model for Testing Agents with Antidepressant Potential

“…This criterion takes into account a theoretical approach to the development of depressive disorders [ 29 , 31 ]. Long-term preliminary studies on the zebrafish model have revealed that it is possible to use Danio rerio in neurobiological research for designing in vivo models of human diseases associated with disturbed social behavior, including depression and anxiety (which will be described in the next sections of the present paper), but also autism [ 32 , 33 ], obsessive compulsive disorder [ 34 ], attention deficit hyperactivity disorder (ADHD) [ 35 , 36 ], addictions [ 37 , 38 , 39 ], or Alzheimer’s disease [ 40 , 41 ].…”

Cell Kinetics in the Adult Neurogenic Niche and Impact of Diet-Induced Accelerated Aging

“…The nature of the underlying processes is poorly understood, and their contribution to neurodegenerative disorders remains elusive (Poulose et al, 2017; for review, see Gao et al, 2017). Our approach can facilitate the current development of the zebrafish model of neurodegenerative disorders and diabetes (Bhattarai et al, 2017; Dorsemans et al, 2017b; Koehler and Williams, 2018), and help elucidating the mechanisms involved in cognitive aging.…”

Zebrafish and Medaka: Important Animal Models for Human Neurodegenerative Diseases

“…In zebrafish, Nada et al observed some major morphological hallmarks such as mini hemorrhagic transformations or micro-bleeds at the later stages of AD in the OA-induced fish [ 102 ]. Another separate research utilized the OA-treated zebrafish for drug screening [ 103 ]. In this study, researchers found that LKE (lanthionine ketimine-5-ethyl ester), a derivative of a naturally occurring brain sulfur metabolite, can exhibit a neuroprotective function against OA by improving the levels of the brain-derived neurotrophic factor (BDNF), anti-apoptotic kinase pAkt (Ser473), and the transcription factor phospho-cAMP response element-binding protein (pCREB) (Ser133).…”

“…When simultaneously exposed to OA and LKE, the zebrafish were able to successfully perform the learning and memory ability, whereas, when exposed to the OA only, the fish could not demonstrate learning and memorizing ability. This suggests that LKE can inhibit the cognitive impairment triggered by OA [ 103 ].…”