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Brain cells from embryos: two successful mouse implant studies

5 December 2011
Appeared in BioNews 636

Two separate studies have successfully transplanted neurons into the brains of mice. The transplanted neurons are able to send and receive electrical impulses, and can be used to compensate for faulty brain cells, restoring normal function. Both studies sourced the transplanted neurons from embryos – mouse embryos in one case, human embryonic stem cells (hESC) were used in the other – and both reported that the neurons fully integrated the mice's brain circuits.

The successful integration of implanted neurons, and their apparently normal behaviour, raises hope that similar techniques could be used to rewire human brain circuits. It could help develop new treatments for neurological diseases such as Lou Gehrig's, Parkinson's or Huntington's disease.

The first study was led by Dr Jeffrey Macklis of Harvard University in Massachusetts, US, and published in Science. The group extracted neurons from healthy mouse embryos and attached green fluorescent proteins onto them so that they could be easily visualised and located. These were transplanted into leptin resistant mice (referred to as 'db/db mice'). These animals cannot respond to leptin, a hormone which helps control body weight. Db/db mice, or indeed humans, can become dangerously obese.

When the group looked at the transplanted neurons, they found that they were operating normally, exchanging signals with the brain. Additionally, the new neurons responded to leptin. As they integrated successfully with the brain circuit, the group had effectively repaired a faulty part of the mice's brains.

'Here, we've rewired a high-level system of brain circuitry that does not naturally experience neurogenesis [growth of new neurons], and this restored substantially normal function', said Dr Macklis. 'These embryonic neurons were wired in with less precision than one might think, but that didn't seem to matter', added his colleague Dr Jeffrey Flier, the Dean of Harvard Medical School.

The mice that received the transplants weighed about 30 percent less than the db/db mice that hadn't had the surgery. The method could be used as a future therapeutic method for people who are leptin resistant, although the role of leptin resistance in obesity is unclear and it may be that leptin resistance is more a result of obesity rather than a cause.

The authors, though, are optimistic about the future of their work. 'The next step for us is to ask parallel questions of other parts of the brain and spinal cord, those involved with [Lou Gehrig's disease] and with spinal cord injuries. In these cases, can we rebuild circuitry in the mammalian brain? Yes, I believe we can', enthused Dr Macklis.

In the second study, led by Dr Jason Weick at the University of Wisconsin in the US, mice were implanted with neurons that had been grown from hESCs. These were implanted into the hippocampus, a region of the brain which deals with navigation and movement, and were also seen to both send and receive electrical impulses in a normal way.

'The big question was can these cells integrate in a functional way', said Dr Weick. 'We show for the first time that these transplanted cells can both listen and talk to surrounding neurons of the adult brain'.

Published in the journal Proceedings of the National Academy of Sciences, the study shows that not only can transplanted neurons integrate themselves with a brain network, but also that those neurons can be derived from stem cells.

Both these studies hint that future treatments for several neurological conditions may include the donation of neurons, which could be hESC-derived. They show that damaged brains are capable of integrating new, healthy neurons, which in turn are capable of functioning properly, thus repairing brain circuits.

Human embryonic stem cell-derived neurons adopt and regulate the activity of an established neural network
PNAS |  21 November 2011
Implanted neurons, grown in the lab, take charge of brain circuitry
EurekAlert! |  21 November 2011
Neurons Created from Embryonic Stem Cells Offers Hope for Damaged Brain Cells
International Business Times |  24 November 2011
Neuron transplant in damaged brain fixes obesity
New Scientist |  24 November 2011
Rebuilding the brain's circuitry
EurekAlert! |  24 November 2011
Researchers rebuild the brain's circuitry
Medical Xpress |  24 November 2011
Transplanted Hypothalamic Neurons Restore Leptin Signaling and Ameliorate Obesity in db/db Mice
Science |  25 November 2011
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