Manipulation of Endogenous Neural Stem Cells as a Therapeutic Strategy for Neurodegenerative Diseases: Insights from Animal Models
Pp. 43-79 (37)
Anna Patten, Patricia S. Brocardo and Joana M. Gil-Mohapel
The mammalian brain retains the capacity to generate new neurons
throughout adulthood through a process referred to as adult neurogenesis. This capacity
is restricted to well-defined brain regions, namely the sub-ventricular zone (SVZ)
adjacent to the lateral ventricles, and the sub-granular zone (SGZ) of the hippocampal
dentate gyrus (DG). Adult neurogenesis and each one of its phases are tightly regulated
and can be influenced by multiple behavioral, physiological, and pathological factors.
Indeed, mounting evidence from animal models has indicated that neurodegenerative
conditions such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and
Huntington’s disease (HD) may be associated with altered neurogenic function.
Importantly, alterations in adult hippocampal neurogenesis may be responsible, at least
in part, for some of the cognitive deficits observed in animal models of these
neurodegenerative conditions as well as individuals afflicted with these disorders. On
the other hand, since adult neural progenitors have been proposed as an endogenous
source of healthy neurons, it has been suggested that harnessing the endogenous
neurogenic capacity in the diseased brain might be of therapeutic value for these
neurodegenerative conditions. In this chapter we review the results obtained in rodent
models of AD, PD, and HD with regards to therapies aimed at restoring adult
neurogenesis and discuss whether such therapies might have therapeutic relevance for
the treatment of these devastating neurodegenerative disorders.
Adult neurogenesis; Alzheimer’s disease, environmental enrichment,
Huntington’s disease, Parkinson’s disease, pharmacological strategy, physical
Division of Medical Sciences, Island Medical Program, University of Victoria, Victoria, B.C., V8W 2Y2, Canada.