Seven Things in Common with a Zebrafish

Fish brains are much more organized than perhaps you have ever imagined, in fact, they share some important similarities to humans that can be studied much more easily in zebrafish.

Our brain allows us to do amazing things like think, feel and imagine, but it is really just a massive web of chemical interactions.   Fish may or may not be able to daydream but their brains share many similarities to humans.  Zebrafish brain development uses the same set of genes that control human brain growth and the fish and human brains are organized in similar ways.  But the zebrafish brain develops in two days compared with the nine months of human development and it is this rapid growth that allows researchers to easily study the formation of the brain. 

We can use zebrafish to study how this hugely complex organ develops, how neural connections are made and what things can go wrong in the brain.  In fact, advancements have been made in treatments for diseases affecting brain development using fish.  Scientists have identified a fish model of Menkes syndrome, a rare disorder affecting brain and neural development, and have been able to cure Menkes in fish by using technology that could one day be used in human patients.  

Upside-down swimming fish are both amusing and educational – researchers are studying these fish to learn how both fish and humans develop a sense of balance.

If a fish is belly up. it is time for a flush, right?  Maybe not - zebrafish that have lost their sense of balance swim upside down.  Otoliths are literally ‘ear-stones’ and are responsible for sensing any shift in head position or movement.  Humans have similar structures called otoconia deep inside the inner ear that are required to transmit information about head movement to the sensory hairs and eventually to our brain.

Upside-down swimming fish are pretty easy to find in a fish tank so researchers are using zebrafish as a model to study how fish and human ear-stones form.  Otoliths are formed by crystals of calcium carbonate, or chalk, embedded with a bunch of proteins.  Zebrafish starmaker mutants have misformed otoliths making them function incorrectly and the fish lose their sense of balance.

Balance disorders can occur in humans as well, especially as we age, and research into zebrafish can help determine why humans lose their sense of balance.  There are also some medications whose side effects are hearing loss and balance problems.  Scientists can now use zebrafish to determine the potential side effects of new human drugs.

Zebrafish may hold the cure to many devastating human illness like muscular dystrophy because fish muscle cells can regenerate; if scientists can find out how fish do this, they may be able to encourage human muscle cells to regenerate as well. 

The tiny zebrafish, Danio rerio relies on its skeletal muscles to power its swimming.  The structure of fish muscles is very similar at the molecular level to our biceps, abdominals and the rest of our muscles.  Most vertebrates share similar muscle structures but no other vertebrate model organism can replicate as quickly as zebrafish allowing researchers to look at muscle development in lots of living fish.  

Despite the molecular similarities, zebrafish muscle can do something human muscles cannot – regenerate.  Research into how muscles in fish regenerate is providing clues into the basics of muscle development as well as pointing researchers towards genes that can be turned on or off to allow muscle regeneration in humans.

If muscles could regenerate, diseases like dystrophies and myopathies could be cured.  Mutations in the dystrophin gene causes Duchenne’s Muscular Dystrophy (DMD) and affects 1 in every 3500 males worldwide; this debilitating condition is lethal and at present there is no cure.  Zebrafish dystrophin mutants (sapje) also have similar muscle degeneration and this allows researchers to use these mutant fish to study how the disease progresses as well as rapidly test possible drugs.  

Everyone has to sleep or it is damaging to our health – but why we sleep and how it is controlled remains to be answered, scientists are using zebrafish to begin to address some of these complex questions.

Despite having no eyelids, no comfy beds or lullabies, fish can get a good night’s sleep.  Determining if fish are sleeping is not as easy as listening for snoring but a team of researchers at Stanford have shown that fish have the same biological characteristics of sleep that humans have.  

The question of whether fish sleep or not has been around since the early 1930s but it has taken scientists almost 80 years to determine if this behavior was, in fact, sleep.  The features of a fish catching some Zs are similar to our own sleep patterns – the fish move less, are harder to arouse and show a place preference for their bed.  

Why and how the brain controls sleep is still a mystery, we know that we need to sleep or else we can get sick or even have a shorter life span. There are both human and fish mutants that have insomnia and these mutant fish sleep 30% than the average. We also know that human sleep patterns rely on hormonal changes to control our circadian rhythm.  Fish have similar hormones, called orexins that control sleep; fish with mutations in this brain chemical sleep much less than average.  Humans and dogs that are missing the same gene can often suffer from excessive sleeping meaning that the gene identified has opposite effects in fish versus humans.  Even though the chemicals involved may have different roles the fact that more and more types of animals can sleep is showing how important our nightly shut-eye is in our evolution.  

Bowel disorders are very common conditions in humans and research is being done on the transparent zebrafish to begin to understand the complex interactions of bacteria and the digestive tract that contribute to bowel health.

Inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis affect over 5 million people worldwide.  There are also millions of tiny zebrafish struggling with their own form of IBD.  Zebrafish can be used as a model for human bowel diseases because they are see-through that lets researchers study their gut without dissections or complicated imaging equipment.  

Recent studies in fish indicate that bowel diseases may result from a change in the balance of the normal microorganisms that exist in your gut.  Some of the zebrafish more susceptible to inflammatory bowel diseases lack a particular enzyme called IAP.   IAP is an alkaline phosphatase or an enzyme that can detoxify a bacterial toxin.  The researchers suggest that individuals with low IAP levels may be more prone to inflammatory bowel diseases because they can’t regulate the balance of bacteria in the gut. 

Fish have become a popular model for bowel diseases because they provide an easy way to test tons of different drugs quickly and on lots of animals.  Plus, the transparency of zebrafish means that they don’t have any shame revealing problems that humans may be less inclined to share.   

For all of us who have realized that working all night before a deadline just doesn’t work – new studies on the zebrafish is telling us that our sleep hormone interferes with memory formation.

Most students are guilty of at least one all-night study session but we’ve been told over and over again that cramming just doesn’t work.  Studies in the small tropical zebrafish are telling us why.  Fish can remember to follow a pattern of light, just like humans can remember their path home after work. But, if these fish received a hormone that normally promotes sleep, they forget their task. 

Melatonin is a hormone in both fish and humans that helps control the circadian rhythm or the sleep-wake cycle.  If fish were given this hormone, their ability to remember was disrupted and the fish trained at night remembered even less.  This may mean that our teachers and parents were right – you can’t remember things you learn at night; not because you’re being irresponsible, but because of melatonin.

There is one thing that humans and zebrafish share that isn’t necessarily in our genes – a love of sushi!  Zebrafish are too small to be a menu item but their voracious appetite for brine shrimp, tuna or good old fashioned fish flakes would make for a good customer in any restaurant.