The therapeutic potential of endogenous hippocampal stem cells for the treatment of neurological disorders

Abstract

While it is now well-established that resident populations of stem and progenitor cells drive neurogenesis in the adult brain, a growing body of evidence indicates that these new neurons play a pivotal role in spatial learning, memory, and mood regulation. As such, interest is gathering to develop strategies to harness the brain's endogenous reservoir of stem and progenitor cells, with the view that newborn neurons may help overcome the loss of neural and cognitive function that occurs during neurodegenerative disease and psychiatric illness. Here we review evidence for the presence of endogenous stem cell populations in the adult hippocampus, especially large pools of latent stem and precursor cells, and the ways in which these populations can be stimulated to produce new neurons. While the translation of this research from animal models to human application is still in its infancy, understanding in detail the cellular and molecular mechanisms that regulate endogenous neurogenesis, offers the potential to use this innate reservoir of precursors to produce neurons that may be able to mitigate against cognitive decline and mood disorders.

Keywords: endogenous adult neurogenesis; hippocampus; neural precursor cell; neural stem cell; stem cell therapy.

Figure 1

Activation of the endogenous population of quiescent stem cells in the adult hippocampus as a therapeutic strategy for neural injury and disease. Enhancement of neurogenesis, through activation of the quiescent stem cell pool, may facilitate neuronal repair and recovery of cognitive function following aging, neuronal disorders, psychiatric conditions, and neurodegenerative diseases. For instance, neuronal activity, such as that which occurs during learning, the induction of long-term potentiation (LTP) and in vitro depolarization, potently activates quiescent stem cell proliferation. A different subpopulation of stem cells is activated following exposure to norepinephrine (NE), and it is thought that this population responds to NE-mediated antidepressant treatment which can alleviate clinical depression. Patterns of electrical stimulation, such as deep brain stimulation and electroconvulsive shock, which are currently used to treat many neurodegenerative and psychiatric conditions in human patients, have also been shown to promote proliferation in animal models. Newborn neurons arising from the distinct progenitor cell pools may have differential roles in the functional outcome of neurodegenerative disease and psychiatric illness. Abbreviations: NE, norepinephrine; LTP, long-term potentiation.