Zebrafish model to treat common neurological disorder

Researchers have found that the learning and memory components of disorder neurofibromatosis (NF1), a genetic disease, are distinct features that are likely to need different treatment approaches.

NF1 is characterised by tumours, attention deficits and learning problems. It is one of the most common inherited neurological disorders, affecting about one in 3,000 people.

"We now know that learning and memory defects in NF1 are distinct and potentially amenable to drug therapy," said co-senior author Jon Epstein from the University of Pennsylvania in the US.

For the study, researchers used a zebrafish model of NF1.

Most people with NF1 have symptoms before the age of 10. Therapies target Ras, a protein family that guides cell proliferation.

Unexpectedly, the researchers showed that some of the behavioural 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.

Memory defects - such as being unable to recall a learned task - can be corrected by drugs that target Ras, while learning deficits are corrected by modulation of the cAMP pathway, the researchers said.

"Our data convincingly show that memory defects in mutant fish are due to abnormal Ras activity, but learning defects are completely unaffected by modulation of these pathways. Rather these deficits are corrected with medicines that modulate cAMP," Epstein said.

The study appeared in the journal Cell Reports.