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

Diana M. Sama, Christopher M. Norris

Research output: Contribution to journalReview articlepeer-review

72 Citations (SciVal)

Abstract

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 Ca2+ dyshomeostasis, through elevation of intracellular Ca2+, 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, Ca2+ and neuroinflammatory signaling mechanisms exhibit extensive cross-talk and bidirectional interactions. For instance, cytokine production in glial cells is strongly dependent on the Ca2+ 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 Ca2+ channels in neurons, leading to Ca2+ dysregulation, hyperactive calcineurin activity, and synaptic depression. Thus, in addition to discussing unique contributions of Ca2+ dyshomeostasis and neuroinflammation, this review emphasizes how these processes interact to hasten age-related synaptic changes.

Original languageEnglish
Pages (from-to)982-995
Number of pages14
JournalAgeing Research Reviews
Volume12
Issue number4
DOIs
StatePublished - Sep 2013

Bibliographical note

Funding Information:
Work supported by NIH grants AG02729 (CMN), AG000242 (DMS), and an award from the Kentucky Spinal Cord and Head Injury Research Trust (CMN) .

Keywords

  • Aging
  • Ca
  • Cytokine
  • Neuroinflammation
  • Plasticity
  • Synapse

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Aging
  • Molecular Biology
  • Neurology

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