Long-Term Impact of Early-Life Stress on Hippocampal Plasticity: Spotlight on Astrocytes

Int J Mol Sci. 2020 Jul 15;21(14):4999. doi: 10.3390/ijms21144999.

Abstract

Adverse experiences during childhood are among the most prominent risk factors for developing mood and anxiety disorders later in life. Early-life stress interventions have been established as suitable models to study the neurobiological basis of childhood adversity in rodents. Different models such as maternal separation, impaired maternal care and juvenile stress during the postweaning/prepubertal life phase are utilized. Especially within the limbic system, they induce lasting alterations in neuronal circuits, neurotransmitter systems, neuronal architecture and plasticity that are further associated with emotional and cognitive information processing. Recent studies found that astrocytes, a special group of glial cells, have altered functions following early-life stress as well. As part of the tripartite synapse, astrocytes interact with neurons in multiple ways by affecting neurotransmitter uptake and metabolism, by providing gliotransmitters and by providing energy to neurons within local circuits. Thus, astrocytes comprise powerful modulators of neuronal plasticity and are well suited to mediate the long-term effects of early-life stress on neuronal circuits. In this review, we will summarize current findings on altered astrocyte function and hippocampal plasticity following early-life stress. Highlighting studies for astrocyte-related plasticity modulation as well as open questions, we will elucidate the potential of astrocytes as new targets for interventions against stress-induced neuropsychiatric disorders.

Keywords: astrocyte; dorsal hippocampus; early-life stress; gliotransmission; juvenile stress; long-term potentiation; maternal separation; short-term plasticity; tripartite synapse; ventral hippocampus.

Publication types

  • Review

MeSH terms

  • Adverse Childhood Experiences*
  • Animals
  • Astrocytes / metabolism
  • Astrocytes / pathology*
  • Hippocampus / metabolism
  • Hippocampus / physiopathology*
  • Humans
  • Maternal Deprivation
  • Mental Disorders / etiology*
  • Mental Disorders / metabolism
  • Mental Disorders / physiopathology
  • Neuronal Plasticity*
  • Neurotransmitter Agents / metabolism
  • Synaptic Transmission

Substances

  • Neurotransmitter Agents