Early-Life Nutritional Programming of Cognition-The Fundamental Role of Epigenetic Mechanisms in Mediating the Relation between Early-Life Environment and Learning and Memory Process

Abstract

The perinatal period is a window of heightened plasticity that lays the groundwork for future anatomic, physiologic, and behavioral outcomes. During this time, maternal diet plays a pivotal role in the maturation of vital organs and the establishment of neuronal connections. However, when perinatal nutrition is either lacking in specific micro- and macronutrients or overloaded with excess calories, the consequences can be devastating and long lasting. The brain is particularly sensitive to perinatal insults, with several neurologic and psychiatric disorders having been linked to a poor in utero environment. Diseases characterized by learning and memory impairments, such as autism, schizophrenia, and Alzheimer disease, are hypothesized to be attributed in part to environmental factors, and evidence suggests that the etiology of these conditions may date back to very early life. In this review, we discuss the role of the early-life diet in shaping cognitive outcomes in offspring. We explore the endocrine and immune mechanisms responsible for these phenotypes and discuss how these systemic factors converge to change the brain's epigenetic landscape and regulate learning and memory across the lifespan. Through understanding the maternal programming of cognition, critical steps may be taken toward preventing and treating diseases that compromise learning and memory.

Keywords: IUGR; epigenetics; inflammation; learning and memory; leptin; nutritional programming; overnutrition; perinatal; psychiatric disease.

FIGURE 1

A poor early-life diet creates a systemic state characterized by heightened inflammation, as well as leptin and glucocorticoid concentrations. These factors converge to induce epigenetic modifications that disrupt neuronal development and function, ultimately compromising cognitive performance.