Figure 1. Energy Balance and Hippocampal Neurogenesis.

(A) Overnutrition due to excess caloric intake, lipotoxicity, and/or sedentary lifestyle results in decreased neuronal differentiation, reduced synaptic complexity, and increased apoptosis (red X’s) in hippocampal NSC’s. These impairments in AN are, in part, due to leptin and insulin resistance, decreased neurotrophic factors, increased inflammatory cytokines, and increased oxidative damage in the neurogenic niche. (B) Energy balance is promoted by moderate caloric restriction and physical exercise, resulting in augmented neuronal differentiation, increased autophagy (green X’s), improved synaptic complexity, and reduced apoptosis in newborn hippocampal neurons. These neurogenic benefits are mediated, in part, due to increased leptin and insulin signaling, neurotrophic factors, stress resistance, sirtuins, GSK3β signaling, and CREB signaling. (C) Malnutrition due to excessive caloric restriction or poor nutrient intake results in inadequate substrate availability, reduced neuronal differentiation, and increased apoptosis (red X’s) in the hippocampus. These impairments in AN are, in part, due to reduced insulin signaling, decreased BDNF, overactive sirtuins, and excessive cellular stress. Created with BioRender.com.