Study sheds light on brain cells important for memory formation

03 September 2014

Neural stem cells in the hippocampus.

Image: Neural stem cells in the hippocampus.

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 in Neuron.

  • A protein crucial for stem cells to form new nerve cells in a part of the brain that produces memories may help lead to ways to stop the deterioration of memory that occurs with ageing. 
  • Stem cells are immature cells that have not yet developed into the specialised cells that make up our organs and tissues. They are able to generate many different types of cell, such as heart cells or insulin-producing pancreatic cells. Stem cells have the ability to renew, or make identical copies of themselves, almost indefinitely. They have the potential to be used to treat many human diseases. 
  • The research was done by scientists at the Medical Research Council (MRC)'s National Institute for Medical Research in collaboration with colleagues at the Cincinnati Children's Hospital Research Foundation in the USA and the Karolinska Institute in Stockholm, Sweden. The work was supported by the MRC, the Wellcome Trust and the US National Institutes of Health.