In The Field

AAN: Smarter mice

One of the first plenary talks here at the AAN meeting was on stem cell treatments for neurological diseases, given this morning by Steven Goldman of the University of Rochester Medical Center in Rochester, NY. Goldman talked to a bulging conference hall about his labs work on progenitor cells in the brain – cells born in the mammalian brain throughout life that are destined to become neurons or glia. These progenitor cells are a bit like neural stem cells, but their destiny is fixed, and they cannot self-renew in the same way. They’re more common in the brain than you might think – about 3% of cells in the white matter are progenitor cells. The long-range plan is to plug them into the human brain in disorders where they are missing – indeed, a clinical trial of such cells in a condition called Pelizaeus-Merzbacher disease was announced in February this year. This is only the second trial of human neural stem cells for a neurodegenerative disease.

Back at the more fundamental level, Goldman has done lots of experiments to show that in mice receiving injections of human glial progenitor cells at birth, the human cells spread and integrate widely into the white and grey matter of the brain, and grow up acting just like their mouse equivalents, spreading into the correct regions and developing in the right ways. His team were pleased to find they integrated well. But what they found next was a surprise to them, and to today’s gathered audience.

The human progenitor cells are larger, more complex, and have more staying power than mouse progenitor cells in the brains of mice. Which means that over time, the brains of mice injected with these cells are becoming more…human. Goldman’s collaborator (and spouse) Maiken Nedergaard and her team at the Center for Translational Neuromedicine, also at U Rochester, has tested these mice to see if their humanised brains make them smarter. The hu-mice do seem to condition more quickly, and show signs at the molecular level of differences in synaptic connections that suggest they might be cognitively different.

These hu-mice might prove a boon to research. As Goldman pointed out, the takeover of their brains by more powerful human cells might have implications for their use as animal models of human cognition (‘smart mouse’ models do exist: see previous Nature coverage for more). Though for the same reason they may not be such useful models of what happens when you try to replace progenitor cells in a brain – human cells plugged into human brains surely would not exhibit the same pattern of competition with the natives. Nonetheless, I’ll be interested to see what the hu-mice can tell us about what makes us human – and whether glial cells are part of the answer.

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