03 Jul 2000

Transplanted stem cells have provided compelling news stories in recent years, promising regeneration of damaged nervous systems, but another possibility-that the adult brain itself could provide the pluripotent cells to replace damaged neurons-may warrant just as much attention. Writing in Nature, Jeffrey Macklis, Sanjay Magavi, and Blair Leavitt of Harvard University provide evidence that they may have induced undifferentiated cortical cells to become neurons, complete with axon-like projections to appropriate targets.

New neurons are hard to come by in the adult brain. There are only two known examples of neurons being born on a regular basis in the mature mammalian brain-cells formed to replenish parts of the hippocampus and the olfactory bulb. But several observers, including Macklis's group, have noted that new cells are born regularly in the mouse neocortex. In this study, they endeavored to induce new neurons by selectively destroying a subset of cortical neurons, the pyramidal cells that project from the neocortex to the thalamus. While the neurons they had targeted were dying of apoptosis, a fraction (one percent to two percent) of the new cells being born were exhibiting signs that were becoming neurons, presumably in response to the death of the mature neurons. These "neurons" expressed markers found only in early neurons (Hu), migrating neurons (Doublecortin), or mature neurons (NeuN). Indeed, some of these cells had the morphology of pyramidal neurons and, once they had arrived at the cortical layer where neurons had been killed, sent out processes to the appropriate target, the thalamus.

"These results raise the enticing possibility that the brain has a latent capacity for self-repair," write Anders Bjorklund and Olle Lindvall of Lund University in Sweden in an accompanying editorial. However, they caution that there is no evidence yet that the new cells are normal, fully functioning pyramidal cells, much less that they would restore any function lost in the mice.—Hakon Heimer