Bidirectional metabolic regulation of neurocognitive function.

The efficiency of somatic energy metabolism is correlated with cognitive change over the lifespan. This relationship is bidirectional, with improved overall fitness associated with enhanced synaptic function and neuroprotection, and synaptic endangerment occurring in the context of impaired energy metabolism. In this review, we discuss recent advancements in the fields of exercise, dietary energy intake and diabetes, as they relate to neuronal function in the hippocampus. Because hippocampal neurons have energy requirements that are relatively higher than those of other brain regions, they are uniquely poised to benefit from exercise, and to be harmed by diabetes. We view exercise and dietary energy restriction as being associated with enhanced hippocampal plasticity at one end of a continuum, with obesity and diabetes accompanied by cognitive impairment at the other end of the continuum. Understanding the mechanisms for this continuum may yield novel therapeutic targets for the prevention and treatment of cognitive decline following aging, disease, or injury.