Gene discovery provides insights into brain formation

Scientists at Duke University Medical Centre found that the gene, called WRP, plays an important role in the brain and demonstrated how memory and learning are affected if the gene is disrupted. The findings, published in the Journal of Neuroscience, have not only uncovered clues to memory and learning, they also provide insights into a form of mental retardation, the researchers said.

"Human genomics studies have opened the floodgates of information that will benefit people with many different diseases," study author Scott Soderling, an assistant professor in the Duke department of cell biology, said.

"But it is impossible to correct something without knowing what the exact underlying problem is." The researchers already knew from past studies that when WRP is disrupted, there might be a possible link with severe mental retardation. The group conducted experiments using neuronal cells in a lab dish which showed that cells enriched with WRP went on to form many filopodia, finger-like protrusions that neurons use to connect with one another.

Without WRP, neurons ultimately were defective in making filopodia,which meant they could not make the correct number of connections, called synapses. In studies on mice with and without the WRP gene, the researchers were able to see behaviour differences.

In one experiment, they tested normal and WRP-deleted mice for their behaviour in recognising a previously unseen toy versus a familiar toy. A mouse with the gene will typically spend less time investigating a toy it has seen before, but the knockout mice spent the same amount of time each toy, suggesting they don't remember the toy they saw yesterday.

"There was a striking difference between the groups of mice," said Soderling. "The mice without WRP had difficulty learning and didn't display typical memory ability in several experiments." "Because the excitatory synapses that we are studying form their connections right after birth in humans, we think these specific pathways may even provide an opportunity for early intervention after birth," Soderling said. "Abnormalities in these types of synapses have been linked to mental retardation, and also to schizophrenia and foetal alcohol syndrome, where there are abnormalities that could later affect learning and memory."

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