Frank A. Beach Award: Programming of neuroendocrine function by early-life experience: A critical role for the immune system

摘要

Many neuropsychiatric disorders are associated with a strong dysregulation of the immune system, and several have a striking etiology in development as well. Our recent evidence using a rodent model of neonatal Escherichia coli infection has revealed novel insight into the mechanisms underlying cognitive deficits in adulthood, and suggests that the early-life immune history of an individual may be critical to understanding the relative risk of developing later-life mental health disorders in humans. A single neonatal infection programs the function of immune cells within the brain, called microglia, for the life of the rodent such that an adult immune challenge results in exaggerated cytokine production within the brain and associated cognitive deficits. I describe the important role of the immune system, notably microglia, during brain development, and discuss some of the many ways in which immune activation during early brain development can affect the later-life outcomes of neural function, immune function, and cognition. Microglia and many immune molecules are critical for normal brain development. Immune activation during brain development can impact behavior throughout life. The developmental immune history of an individual may predict risk of neuropsychiatric disorders. A model of neonatal infection may inform diverse environmental challenges which impact the developing immune system.