Dormant Neural Precursor Cells May Awaken Over Adult Life to Maintain the Brain

Neural stem cells residing within a few regions of the mammalian brain divide to generate new daughter neurons throughout adult life, the process of neurogenesis. Neurogenesis is particularly associated with functions such as memory, which requires changes in brain state driven by the creation of new neurons and neural connections. Additionally, however, researchers have identified a population of dormant progenitor cells that can mature into neurons, more broadly distributed throughout the brain. This population can be diminished and eventually exhausted by that activity, but researchers hypothesize that it could nonetheless be a source of regenerative capacity for the aging brain if the remaining pool of dormant progenitor cells could be awakened.

More speculatively, this type of progenitor cell might be a good candidate for cell therapies aimed at improving function in the aging brain. If the mechanism of awakening is understood and production of the cell type possible, continual rounds of therapy might be undertakn. Still, such efforts to restore the brain are future concerns: it remains quite challenging to deliver any therapy to the brain, never mind very challenging forms of therapy such as those involving the production and quality control of cells.

The awakening of dormant neuronal precursors in the adult and aged brain

The mammalian brain is traditionally described as a network of neurons and glia, in which maturation and establishment of connectivity occur shortly after birth, followed by circuit refinement throughout the early part of life. Yet, there are exceptions concerning the timing of maturation because specific types of neurons are added progressively to the brain circuits during the adulthood. Some well-known neuronal "latecomers" are those originating from the brain areas designated as adult neurogenic niches.

Recent studies and new technology allowed researchers to update the current concepts of adult neurogenesis by revealing the existence of other types of neuronal precursors, which reside outside the neurogenic niches. Although generated during the embryonic development, these cell types retain post-mitotic immaturity until adulthood. During adulthood, such neuronal precursors, herewith referred to as "dormant precursors," eventually awaken and become adult-matured neurons (AM). Much about the awakening and maturation of dormant precursors is yet to be revealed. So far, several works in different mammalian species suggested that dormant precursors occupy numerous brain regions.

We previously demonstrated that, after awakening, dormant precursors undergo axonal sprouting, formation of synapses, and the progressive acquisition of functional input and output during the transition from precursor to AM. At the same time, we were puzzled to note that while many dormant precursors undertook the course of maturation during early adulthood, some cells remained immature throughout adulthood. Similar observation was also common in other mammalian species, including primates and humans.

Consequently, we questioned whether the precursors remaining dormant for most of a lifetime can actually eventually awake and follow a course of late maturation or whether they fail to awaken altogether. On the one hand, we speculated that the aging of the brain may hinder or completely impair the awakening. On the other hand, if late awakening and maturation were possible, this would imply that the old brain in mammalians is equipped with an unexplored source of young neurons.