Adult neural stem cells in the dentate gyrus of the hippocampus are negatively and positively regulated by a broad range of environmental stimuli that include aging, stress, social interaction, physical activity, and dietary modulation. Interestingly, dietary regulation has a distinct outcome, such that reduced dietary intake enhances neurogenesis, whereas excess calorie intake by a high-fat diet has a negative effect. As a type of metabolic stress, dietary restriction (DR) is also known to extend life span and increase resistance to age-related neurodegenerative diseases. However, the potential application of DR as a "neurogenic enhancer" in humans remains problematic because of the severity of restriction and the protracted duration of the treatment required. Therefore, the authors consider that an understanding of the neurogenic mechanisms of DR would provide a basis for the identification of the pharmacological and nutraceutical interventions that mimic the beneficial effects of DR without limiting caloric intake. The current review describes the regulatory effect of DR on hippocampal neurogenesis and presents a possible neurogenic mechanism.
© 2011 New York Academy of Sciences.