Metabolic defects in mice corrected with transplanted embryonic neurones

A new study has revealed that immature neurones taken from healthy mouse embryos can repair damaged brain circuitry and partially normalise metabolism when transplanted into adult mice that have grown morbidly obese due to a genetic deficiency. This proof-of-principle discovery represents one step down a long road toward neuronal replacement therapy, which researchers hope might one day be used to repair brains that have been injured by trauma or disease.

Artur Czupryn and colleagues took the immature neurones from the hypothalamus of wild-type mouse embryos and transplanted them into the hypothalamus of adult mice lacking a receptor for the hormone, leptin, which is known to regulate body weight. The researchers observed that the donor neurones were able to differentiate into four distinct neuronal types that then formed functional connections in the brains of the obese mice.

Their study appears in the 25 November issue of the journal Science, which is published by AAAS, the nonprofit science society.

'We chose this problem not because, even for a moment, we would pursue the idea of neurone transplantation for the treatment of obesity,' explained Jeffrey Macklis from Harvard University, a corresponding author of the report. 'What we did was take this very complicated circuitry in the hypothalamus that has a very clear, measurable outcome - not only obesity in the mice, but changes in their serum glucose (like diabetic human beings have), changes in their insulin levels and changes in their fat vs. lean body weights - and we used that complex circuitry as a test case for whether precisely selected and controlled neurone transplants could really rewire the brain.'

The transplanted neurones did apparently restore leptin signalling in the brains of the obese mice because the rodents slimmed down and their metabolism began returning to normal levels, according to Czupryn and his colleagues.

'What we found is that these neurones not only turned into the right kinds of cells, but that they sent signals to the recipients' brain and received signals from the recipients' brain,' said Macklis.

Although the researchers say that neuronal replacement is certainly not a practical approach to treating obesity, their study nonetheless provides evidence that the transplantation of donor neurones at the appropriate stage of development can promote functional recovery of a brain region that controls a complex phenotype.