Immune Dysregulation and Cognitive Vulnerability in the Aging Brain: Interactions of Microglia, IL-1β, BDNF and Synaptic Plasticity

Neuropharmacology. 2015 Sep;96(Pt A):11-8. doi: 10.1016/j.neuropharm.2014.12.020. Epub 2014 Dec 27.

Abstract

Older individuals often experience declines in cognitive function after events (e.g. infection, or injury) that trigger activation of the immune system. This occurs at least in part because aging sensitizes the response of microglia (the brain's resident immune cells) to signals triggered by an immune challenge. In the aging brain, microglia respond to these signals by producing more pro-inflammatory cytokines (e.g. interleukin-1beta or IL-1β) and producing them for longer than microglia in younger brains. This exaggerated inflammatory response can compromise processes critical for optimal cognitive functioning. Interleukin-1β is central to the inflammatory response and is a key mediator and modulator of an array of associated biological functions; thus its production and release is usually very tightly regulated. This review will focus on the impact of dysregulated production of IL-1β on hippocampus dependent-memory systems and associated synaptic plasticity processes. The neurotrophin brain-derived neurotrophic factor (BNDF) helps to protect neurons from damage caused by infection or injury, and it plays a critical role in many of the same memory and hippocampal plasticity processes compromised by dysregulated production of IL-1β. This suggests that an exaggerated brain inflammatory response, arising from aging and a secondary immune challenge, may erode the capacity to provide the BDNF needed for memory-related plasticity processes at hippocampal synapses. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'.

Keywords: Aging; BDNF; Cognitive vulnerability; IL-1β; Infection; Inflammation; Memory; Microglia; Synaptic plasticity.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aging / immunology*
  • Aging / metabolism
  • Aging / psychology*
  • Animals
  • Brain / immunology*
  • Brain / metabolism
  • Brain / physiopathology
  • Brain-Derived Neurotrophic Factor / physiology
  • Cognition Disorders / etiology
  • Cognition Disorders / immunology*
  • Hippocampus / immunology
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Humans
  • Inflammation Mediators / physiology
  • Interleukin-1beta / physiology
  • Microglia / physiology*
  • Neuronal Plasticity

Substances

  • Brain-Derived Neurotrophic Factor
  • Inflammation Mediators
  • Interleukin-1beta