Cave fish have long fascinated biologists because of their missing eyes and pale skin. Now a researcher is to study for another reason: Their behavior may provide clues to the genetic basis of some human psychiatric disorders. Last week at the 23rd International Conference on Subterranean Biology in Fayetteville, Arkansas, , he demonstrated how drugs that help people with schizophrenia and autism affect fish likewise.
"I think there is a lot of potential" for these fish to teach us about mental disorders, said David Culver, an evolutionary biologist at the American University in Washington, DC, which has not participated in the study. Culver added that as other work on the cause of blindness cave fish the new research may also have implications for human disease.
There are ten years, the lead author of the new study, Masato Yoshizawa, wanted to understand how the brain by studying the effects of natural selection on behavior. The Mexican tetra ( Astyanax mexicanus ), a fish cave with very similar surface parents, seemed an excellent perspective for this work. Because the two populations can interbreed, it is easier to identify genes that may be related to neural defects underlying behavioral differences. These reproduction studies are not possible in humans.
The blind cave fish differ from their surface relatives of several notable ways. They do not have a social structure, and they are not in school. Instead, they lead a life solitary behavior is logical given their lack of natural predators. They also almost never sleep. They are hyperactive, and, unlike other fish, they are attracted to certain vibrations in the water. Finally, they tend to do the same behavior over and over again and seem to have higher anxiety than their surface relatives.
Yoshizawa, now a biologist evolutionary development at the University of Hawaii, Manoa, tested whether these fish could be useful in understanding the genetic basis of schizophrenia or autism. Studies in animals typical mouse-model-are rarely enlightening, because rodents often behave normally even when the researchers manipulate the genes that should cause these disorders. But even without genetic tinkering, the fish already show some "symptoms" of disease, such as insomnia, hyperactivity and antisocial behavior.
What's more, 0% of 101 genes of traditional risk factors for human psychiatric diseases are also present in the genome of the fish to the cave, according to comparison Yoshizawa of genomes and transcriptomes-surveys genes in fish caves and human assets. A third of these genes are more or less active in the cave fish than they are in the area of fish.
As a first step towards the evaluation of this new model, Yoshizawa and other processed the fish to the cave with several psychiatric drugs. It three years ago, a French team has shown that the antidepressant fluoxetine (commonly known as Prozac) caused the fish to become more aggressive towards each other. Yoshizawa has now shown that fluoxetine-and clozapine is sleep fish swim more and less antipsychotic. "Overall, these drug responses in caves fish are very similar to what you see in human patients", said last week at the meeting of Fayetteville. "This is strong evidence that fish caves could be a good model for human psychiatric disease."
Now he and his colleagues are studying a larger number of cave fish with variation of these behaviors in the hope they can sort out which versions of genes that are associated with extreme behaviors. From there, they intend to investigate how these genes interact with each other and the environment to change the behavior of fish. Combined with an overview of gene expression, nerve connections and imaging of neuronal activity, work could help cut the long list of genes involved in autism and schizophrenia, said Yoshizawa.
Of course, Yoshizawa faces a long road ahead. "Like any model system, the fish of the cave has limits," said Humam Araj, a program officer at the National Eye Institute in Bethesda, Maryland, which has not participated. The fish and humans are separated by 400 million years of evolution, so that the control of these behaviors can not be the same in humans and fish Still, Culver said.. "I think it's really exciting things"
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