3 July 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.
Reference:(1) Magavi SS, Leavitt BR, Macklis JD. Induction of neurogenesis
in the neocortex of adult mice. Nature 2000 June 22;405:951-55. Abstract
(2) Bjorklund A, Lindvall O. Self-repair in the brain. Nature 2000 June;405:892-4.