Ca2+ signaling, mitochondria and sensitivity to oxidative stress in aging astrocytes

Da Ting Lin, Jun Wu, Deborah Holstein, Geeta Upadhyay, Wendy Rourk, Elizabeth Muller, James D. Lechleiter

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Age-related changes in astrocytes that could potentially affect neuroprotection have been largely unexplored. To test whether astrocyte function was diminished during the aging process, we examined cell growth, Ca2+ signaling, mitochondrial membrane potential (ΔΨ) and neuroprotection of NGF-differentiated PC12 cells. We observed that cell growth was significantly slower for astrocytes cultured from old (26-29 months) mice as compared to young (4-6 months) mice. ΔΨs in old astrocytes were also more depolarized (lower) than in young astrocytes and old astrocytes showed greater sensitivity to the oxidant tert-butyl hydrogen peroxide (t-BuOOH). ATP-induced Ca2+ responses in old astrocytes were consistently larger in amplitude and more frequently oscillatory than in young astrocytes, which may be attributable to lower mitochondrial Ca2+ sequestration. Finally, NGF-differentiated PC12 cells that were co-cultured with old astrocytes were significantly more sensitive to t-BuOOH treatment than co-cultures of NGF-differentiated PC12 cells with young astrocytes. Together, these data demonstrate that astrocyte physiology is significantly altered during the aging process and that the astrocyte's ability to protect neurons is compromised.

Original languageEnglish (US)
Pages (from-to)99-111
Number of pages13
JournalNeurobiology of Aging
Volume28
Issue number1
DOIs
StatePublished - Jan 1 2007

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Keywords

  • ATP
  • Ca waves
  • IP
  • Mitochondria
  • Nerve growth factor
  • PC12 cells
  • Two-photon

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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