Protein discovery aids neurone research

Australian researchers have unravelled part of the process controlling the production of new neurones from stem cells in the brain.

The team was headed by Prof Perry Bartlett, who has recently moved his group from Melbourne's Walter and Eliza Hall Institute to the new Institute for Brain Research at the University of Queensland.

The researchers identified the SOCS-2 protein (suppression of cytokine signalling protein 2), which is found in high levels in the brain, as a major regulator of the neural differentiation process in mice.

But the regulation is not through cytokines as expected, but in response to growth hormone, which was not thought to have a role in neural differentiation.

"We've been trying to track down for a long time the key regulatory elements for turning stem cells into neurones," said Bartlett. He explained that his research team had initially determined that over-expression of the SOCS-2 protein caused an increase in the number of neurones being formed from neural progenitor cells, while under-expression resulted in a decrease in the number of neurones.

The researchers thought that the SOCS-2 protein was acting through cytokine regulation, particularly on leukaemia inhibitory factor (LIF) and similar cytokines in the brain, which are involved in the differentiation of neural progenitors into neurones and astrocytes.

"The biggest surprise was that SOCS-2 was regulating growth hormones, not cytokines," explained Bartlett. Growth hormone was not known to have a major role in neural differentiation.

The researchers showed that growth hormone inhibited neural differentiation by down-regulating the expression of Neurogenin I, a major transcription factor involved in neural differentiation, and that SOCS-2 blocked that inhibition, resulting in increased neuronal differentiation.

The next step, according to Bartlett, is to investigate how this process can be used to stimulate conversion of stem cells into neurones in vivo.

"We could look for the molecule leading to the drug that would stimulate SOCS-2 to more actively suppress growth hormone. Alternatively, we could seek new molecules that would block the action of growth hormone. Either way, the inactivation of growth hormone in the adult neural stem cell is the key to the production of new nerve cells," Bartlett said.

The SOCS-2 protein was discovered at WEHI a number of years ago, and has been licensed to Amrad for development.

According to Bartlett, this discovery could have implications for the treatment of ageing with growth hormones, an idea that has gained popularity in recent years.

"It goes against the idea that growth hormones prevent ageing," he said. The research was published online last week in Nature Neuroscience and can be accessed at http://dx.doi.org/10.1038/nn954