Zebrafish model of a learning and memory disorder shows better way to target treatment

Using a zebrafish model of a human genetic disease called neurofibromatosis (NF1), a team from the Perelman School of Medicine at the University of Pennsylvania has found that the learning and memory components of the disorder are distinct features that will likely need different treatment approaches. They published their results this month inCell Reports.

NF1 is one of the most common inherited neurological disorders, affecting about one in 3,000 people. It is characterized by tumors, attention deficits, and learning problems. Most people with NF1 have symptoms before the age of 10. Therapies target Ras, a protein family that guides cell proliferation. The NF1 gene encodes neurofibromin, a very large protein with a small domain involved in Ras regulation.

Unexpectedly, the Penn team showed that some of the behavioral defects in mutant fish are not related to abnormal Ras, but can be corrected by drugs that affect another signaling pathway controlled by the small molecule cAMP. They used the zebrafish model of NF1 to show that memory defects – such as the recall of a learned task—can be corrected by drugs that target Ras, while learning deficits are corrected by modulation of the cAMP pathway. Overall, the team's results have implications for potential therapies in people with NF1.

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The Pig, the Fish and the Jellyfish: Tracing Nervous Disorders in Humans

Oct. 17, 2013 — What do pigs, jellyfish and zebrafish have in common? It might be hard to discern the connection, but the different species are all pieces in a puzzle. A puzzle which is itself part of a larger picture of solving the riddles of diseases in humans.

The pig, the jellyfish and the zebrafish are being used by scientists at Aarhus University to, among other things, gain a greater understanding of hereditary forms of diseases affecting the nervous system. This can be disorders like Parkinson's disease, Alzheimer's disease, autism, epilepsy and the motor neurone disease ALS.

In a project, which has just finished, the scientists have focussed on a specific gene in pigs. The gene, SYN1, encodes the protein synapsin, which is involved in communication between nerve cells. Synapsin almost exclusively occurs in nerve cells in the brain. Parts of the gene can thus be used to control an expression of genes connected to hereditary versions of the aforementioned disorders.

The pig

The SYN1 gene can, with its specific expression in nerve cells, be used for generation of pig models of neurodegenerative diseases like Parkinson's. The reason scientists bring a pig into the equation is that the pig is well suited as a model for investigating human diseases.

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Schooling Fish: Wild Zebrafish Assess Risk Through Social Learning

ScienceDaily (June 19, 2012) — Individuals in some species learn information about food, predators, and potential mates indirectly from conspecifics, without taking unnecessary risks by learning directly for themselves ('social learning'). Sarah Zala and Dustin Penn from the Konrad Lorenz Institute of Ethology of the University of Veterinary Medicine, Vienna investigated whether zebrafish use social learning to assess risk ('boldness/shyness' behaviour). They found that wild zebrafish, which are more timid than their domesticated counterparts, became emboldened after interacting with domesticated zebrafish. The opposite did not occur, however. When the bolder domesticated zebrafish came in contact with wild zebrafish, they did not become more cautious.

The study is published in the current issue of the journal Animal Behaviour.

To test fish disposition, the scientists scored "boldness" as the response to a moving object. If fish approached the object relatively closely, they were classified as "bold," while those who tended to stay at the back of the tank were considered "shy." When the wild fish were allowed to interact with bolder domesticated fish, they became less likely to avoid the moving object.

These results confirm the researchers´ hypothesis that zebrafish use social learning for assessing risk: they observe other individuals' behaviour, and change their own behaviour accordingly. The findings also indicate that zebrafish adapt their social-learning strategies to the costs of a perceived risk, as the domesticated bold fish did not change their behaviour after interacting with the shy fish.

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  http://www.sciencedaily.com/releases/2012/06/120619103849.htm

Better Housing Conditions for Zebrafish Could Improve Research Results

ScienceDaily (May 3, 2012) — Changing the conditions that zebrafish are kept in could have an impact on their behaviour in animal studies and the reliability of results, according to scientists from Queen Mary, University of London.

Zebrafish, like rats and mice, are often used by neuroscientists to explore mechanisms controlling behaviour and in the search for new compounds to treat behavioural disease such as addiction, attention deficit disorders or autism.

It is known that housing and handling affects the results of behavioural studies done in rats and mice, but until now there have been few studies of how the environment the fish are kept in before they are tested can impact on the results.

Writing in the journal PLoS One, Dr Caroline Brennan from Queen Mary's School of Biological and Chemical Sciences explains: "Practical considerations make zebrafish a very useful species in which to explore mechanisms controlling behaviour. Their small size (less than 2 cm) and prolific breeding (approx. 300 eggs per pairing) makes it easy and cheap to keep large numbers of zebrafish in a small space. It is also relatively easy to change the zebrafish genome to explore how changes in different genes affect behaviour.

"As fish have many proteins and brain circuits in common with humans, factors that affect the fish behaviour can tell us about things that may affect human behaviour."

Continued:  http://www.sciencedaily.com/releases/2012/05/120503120500.htm