Calcium dysregulation and neuroinflammation: discrete and integrated mechanisms for age-related synaptic dysfunction

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Some of the best biomarkers of age-related cognitive decline are closely linked to synaptic function and plasticity. This review highlights several age-related synaptic alterations as they relate to Ca(2+) dyshomeostasis, through elevation of intracellular Ca(2+), and neuroinflammation, through production of pro-inflammatory cytokines including interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). Though distinct in many ways, Ca(2+) and neuroinflammatory signaling mechanisms exhibit extensive cross-talk and bidirectional interactions. For instance, cytokine production in glial cells is strongly dependent on the Ca(2+) dependent protein phosphatase calcineurin, which shows elevated activity in animal models of aging and disease. In turn, pro-inflammatory cytokines, such as TNF, can augment the expression/activity of L-type voltage sensitive Ca(2+) channels in neurons, leading to Ca(2+) dysregulation, hyperactive calcineurin activity, and synaptic depression. Thus, in addition to discussing unique contributions of Ca(2+) dyshomeostasis and neuroinflammation, this review emphasizes how these processes interact to hasten age-related synaptic changes.

Original languageEnglish
Pages (from-to)982-95
Number of pages14
JournalAgeing Research Reviews
Issue number4
StatePublished - Sep 2013

Bibliographical note

Copyright © 2013 Elsevier B.V. All rights reserved.


  • Aging/physiology
  • Animals
  • Calcium/physiology
  • Humans
  • Inflammation/metabolism
  • Inflammation Mediators/metabolism
  • Long-Term Potentiation/physiology
  • Long-Term Synaptic Depression/physiology
  • Neuronal Plasticity/physiology
  • Neurons/metabolism
  • Signal Transduction/physiology
  • Synapses/physiology


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