Stem cells in the hippocampus, a part of the brain that produces
memories, continuously divide and generate new nerve cells. These
play an important role in memory formation.
Now, scientists at the Medical Research Council's National
Institute for Medical Research (NIMR; now part of the Francis
Crick Institute) have discovered that a protein called Ascl1
is crucial for this process to happen.
Nerve cell production has previously been shown to decline in
old age and is linked to deterioration of memory. The current study
has the potential to help understand this link and to design
methods to prevent the loss of nerve cells.
The NIMR team led by Dr François Guillemot examined the
production of Ascl1 protein in hippocampal stem cells in mice and
looked at what happened to stem cell division and nerve cell
production when they eliminated the protein. They also used
cultures of hippocampal stem cells grown in the lab to find out how
Ascl1 controls stem cell division.
The scientists discovered that the division of hippocampal stem
cells and the production of new nerve cells are stimulated by the
production of Ascl1, which occurs in response to external stimuli.
They also found that Ascl1 production is absolutely necessary for
stem cell division and for nerve cell generation - when the protein
was eliminated, the stem cells were unable to divide at all.
The results showed that Ascl1 promotes stem cell division and
growth by directly regulating a number of genes involved in
regulating the cell cycle.
Dr Guillemot said: "This is the first time a mechanism that
controls the activity of brain stem cells in response to external
stimuli has been identified."
He added: "A striking feature of hippocampal stem cells in
mice is that their rates of division and nerve cell production
decline rapidly as animals age. This decline of stem cell activity
has been shown to contribute to the deterioration of memory in old
mice.
"Our findings will help understand the link between stem cell
activity and old age and will help design methods to prevent the
age-related reduction of nerve cell production, first in animals
and eventually in humans."
The paper, A transcriptional mechanism integrating inputs from extracellular
signals to activate hippocampal stem cells, is published inNeuron.