Abstract
New neurons incorporate into the granular cell layer of the dentate gyrus throughout life. Neurogenesis is modulated by behavior and plays a major role in hippocampal plasticity. Along with older mature neurons, new neurons structure the dentate gyrus, and determine its function. Recent data suggest that the level of hippocampal neurogenesis is substantial in the human brain, suggesting that neurogenesis may have important implications for human cognition. In support of that, impaired neurogenesis compromises hippocampal function and plays a role in cognitive deficits in Alzheimer's disease mouse models. We review current work suggesting that neuronal differentiation is defective in Alzheimer's disease, leading to dysfunction of the dentate gyrus. Additionally, alterations in critical signals regulating neurogenesis, such as presenilin-1, Notch 1, soluble amyloid precursor protein, CREB, and β-catenin underlie dysfunctional neurogenesis in Alzheimer's disease. Lastly, we discuss the detectability of neurogenesis in the live mouse and human brain, as well as the therapeutic implications of enhancing neurogenesis for the treatment of cognitive deficits and Alzheimer's disease.
Highlights
In early development neurons are rapidly produced to form the intricate complexity of the brain and peripheral nervous system
In support of the role of hippocampal neurogenesis in plasticity, learning and memory, increasing evidence suggests that cognitive deficits, difficulty learning new information and memory loss, as occurs in Alzheimer’s disease (AD), may be, at least in part, due to impairments in adult neurogenesis (Demars et al, 2010, 2013; Lazarov and Marr, 2010; Lazarov et al, 2010)
A recent study suggests that there is a moderate decline in neurogenesis with aging (Spalding et al, 2013). As of yet, it is unclear how this decline impacts cognitive function in humans or whether similar memory paradigms are regulated by adult neurogenesis as they are in rodents
Summary
In early development neurons are rapidly produced to form the intricate complexity of the brain and peripheral nervous system. In support of the role of hippocampal neurogenesis in plasticity, learning and memory, increasing evidence suggests that cognitive deficits, difficulty learning new information and memory loss, as occurs in Alzheimer’s disease (AD), may be, at least in part, due to impairments in adult neurogenesis (Demars et al, 2010, 2013; Lazarov and Marr, 2010; Lazarov et al, 2010).
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