Zebrafish, Medaka And Turquoise Killifish For Understanding Human Neurodegenerative/Neurodevelopmental Disorders Part 1

Mar 27, 2024

Abstract: 

In recent years, small fishes such as zebrafish and medaka have been widely recognized as model animals. They have high homology in genetics and tissue structure with humans and unique features that mammalian model animals do not have, such as transparency of embryos and larvae, small body size, and ease of experiments, including genetic manipulation. 

The connection between genetics and memory is an emerging area of research, and some studies suggest that our memories are closely linked to our genes. From this perspective, we can draw the following conclusions when looking at how genetics affects human memory.

First, genetic material can affect the physiological structure and working mode of the human brain through the coding of genes. These changes, in part, affect our ability to form and retain memories. For example, some people are born with better working memory, and a greater ability to transition from short-term to long-term memory. This memory ability is often related to the presence of specific gene monomers. Similarly, some genes may make humans more susceptible to problems such as amnesia, which can directly affect human memory performance.

Secondly, environmental factors can also affect human memory performance together with genetic factors. Even people with the same genetic background will have different memory performance under different education and training methods. For example, long-term training experience can greatly improve memory. This training process can last for months or years, which means that the impact of environmental factors on memory performance is also important.

Whether it's due to biological foundations or environmental factors, there are things we can do to improve our memory performance through research and some practical steps. We can enhance our memory performance by reading, reviewing, practicing, etc., and by exploring the interaction of these factors, we can understand these processes more fully.

Overall, the link between genetics and memory is an emerging field of science that offers a new way to learn more about how the human brain works. Understanding this knowledge can help us better grasp the nature of memory and take appropriate steps to improve our personal memory performance. Let's harness this knowledge and practice it in our daily lives to help us become smarter, more confident, and more successful people. It can be seen that we need to improve memory, and Cistanche deserticola can significantly improve memory, because Cistanche deserticola has antioxidant, anti-inflammatory, and anti-aging effects, which can help reduce oxidation and inflammatory reactions in the brain, thereby protecting the health of the nervous system. In addition, Cistanche deserticola can also promote the growth and repair of nerve cells, thereby enhancing the connectivity and function of neural networks. These effects can help improve memory, learning, and thinking speed, and may also prevent the development of cognitive dysfunction and neurodegenerative diseases.

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Zebrafish and medaka have been used extensively in the field of neurology, especially to unveil the mechanisms of neurodegenerative diseases such as Parkinson's and Alzheimer's disease, and recently, these fishes have also been utilized to understand neurodevelopmental disorders such as autism spectrum disorder. 

The turquoise killifish has emerged as a new and unique model animal, especially for aging research due to its unique life cycle, and this fish also seems to be useful for age-related neurological diseases. 

These small fishes are excellent animal models for the analysis of human neurological disorders and are expected to play increasing roles in this field. Here, we introduce various applications of these model fishes to improve our understanding of human neurological disorders.

Keywords: small fish; zebrafish; medaka; turquoise killifish; neurodegenerative disease; Parkinson's disease; aging; neurodevelopmental disorder.

1. Introduction

When we think of model animals used in medical research, the typical animal is a mouse. Throughout the history of science, many researchers have standardized and advanced experimental procedures using mice, including genetic techniques, biochemical analysis, and behavioral analysis. There is no doubt that mice are at the forefront of model animals. 

In addition to mice, rats, flies and nematodes have a relatively long history as model animals. Among model animals, small fishes such as zebrafish (Danio rerio), medaka (Oryzias latipes), and turquoise killifish (Nothobranchius furzeri) are relative newcomers but are increasingly present (Table 1) [1–7]. 

Because fish and mammals, such as humans, diverged so recently in the course of evolution, their anatomical and genetic homologies are remarkably well preserved. In the laboratory, small fishes are excellent model animals with many advantages that mammalian models do not have, such as simple maintenance from embryo to adult, excellent tissue visibility with transparent embryos and larvae, easy handling in laboratory experiments, including molecular biology, biochemistry, histology and so on. 

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This review outlines the characteristics of these small fishes, their relevance to humans, the benefits of using small fishes as model animals for neurological disorders, and how small fishes are currently being used in research for neurodegenerative diseases and neurodevelopmental disorders.

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2. Central Nervous System in Small Fishes

Flies and nematodes, which are used as small model animals, are invertebrates and may be disadvantageous when considered as human disease models. On the other hand, small fishes are vertebrates such as mice and humans, and many of their organ structures are similar to those of humans. 

The basic structure and function of the central nervous system is conserved from small fishes to humans. In nematodes, for example, the ganglia of the head are sometimes referred to as the "brain", but they have no direct phylogenetic relationship to the vertebrate brain. 

Small fishes, on the other hand, have what can accurately be called a brain. Although there are some differences between the brains of small fishes and humans, they are anatomically and functionally similar as a whole. 

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This section describes the anatomical characteristics of the zebrafish brain. An excellent phylogenetic tree of the evolutionary connections among the model animals mentioned above is given in a previous report [6]. 

The structural and anatomical formation of the central nervous system in zebrafish begins early in development. After the formation of the neural tube at 17 hpf (hours post-fertilization), brain morphogenesis begins. 

The boundary between the midbrain and hindbrain begins to form, and regions such as the cerebellum and thalamus are developed [8]. Human dopaminergic neurons in the substantia nigra are located in the midbrain, but there are no dopaminergic clusters in the anatomically classified midbrain of zebrafish. There are several clusters of dopaminergic neurons in the neighboring diencephalon, and their formation has begun at 18 hpf [9]. 

Furthermore, it has been shown that some of the dopaminergic neurons in this diencephalon extend and project long axons to the striatum, and these neurons could be equivalent to human dopaminergic neurons in the substantia nigra [10]. 

Dopaminergic projections to the forebrain in zebrafish are thought to be homologous to the reward system in mammals [11]. Since the overall composition of dopaminergic neurons is conserved among teleosts, the distribution of dopaminergic neurons in turquoise killifish is similar to zebrafish and medaka. 

Please refer to the latest report on the analysis of catecholaminergic neurons in the central nervous system of turquoise killifish [12].

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