Though the majority of our neurons are formed before we are born and don’t regenerate as we go through life, a brain region called the hippocampal dentate gyrus – which is largely responsible for memory – does continue to produce new neurons throughout our lifetime. These new cells are derived from neural stem cells (NSCs), and are vital for the maintenance of our cognitive capacities as we age, although until now scientists had struggled to explain how these NSCs develop into fully functioning neurons.
At the heart of the mystery is the fact that these stem cells aren’t predestined to become neurons, but can instead develop into other types of brain cells such as astrocytes and oligodendrocytes. Both of these are examples of glial cells, which surround neurons and help to protect and support them. However, in the hippocampus, all NSCs do go on to become neurons, and none produce oligodendrocytes.
Until now, it had been largely accepted that stem cells do not control their own destiny, and are instead stimulated to develop a particular type of cell by specific compounds in their external environment. However, a new study in the journal Cell Stem Cell reveals that NSCs in the hippocampus are in fact masters of their own destiny, and contain internal mechanisms that steer their development in favor of becoming neurons rather than glial cells.
Oligodendrocytes are glial cells that surround and support neurons. Designua/Shutterstock
The study authors bred mice to lack an enzyme called Drosha in their hippocampal stem cells, and found that this caused them to produce oligodendrocytes rather than neurons. The function of Drosha is to eliminate sections of micro RNA that control the activity of the transcription factor nuclear factor IB (NFIB), which in turn regulates the expression of certain genes that determine what type of cell an NSC becomes.
This led the researchers to suspect that NFIB must play a major role in driving the development of NSCs into glial cells instead of neurons, and that Drosha prevents this from occurring by inhibiting NFIB. To confirm this, the team then bred mice that lacked NFIB, and found that this restored the ability of their NSCs to develop into neurons rather than oligodendrocytes.
The creation of new neurons from NSCs – or neurogenesis – is vital for the maintenance of cognitive function, and age-related disruptions to this process have been associated with the onset of dementia. Understanding how neurogenesis works could therefore prove to be the first step in the development of new treatments for a range of cognitive disorders.