Brain region-specific, age-related, alterations in mitochondrial responses to elevated calcium

Maile R. Brown, James W. Geddes, Patrick G. Sullivan

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

An age-related Ca 2+ dysregulation and increased production of reactive oxygen species (ROS) may contribute to late-onset neurodegenerative disorders. These alterations are often attributed to impaired mitochondrial function yet few studies have directly examined mitochondria isolated from various regions of the aged brain. The purpose of this study was to examine Ca 2+-buffering and ROS production in mitochondria isolated from Fischer 344 rats ranging in age from 4 to 25 months. Mitchondria isolated from the cortex of the 25 month rat brain exhibited greater rates of ROS production and mitochondrial swelling in response to increasing Ca 2+ loads as compared to mitochondria isolated from younger (4, 13 month) animals. The increased swelling is indicative of opening of the mitochondrial permeability transition pore indicating impaired Ca 2+ buffering/cycling in aged animals. These age-related differences were not observed in mitochondria isolated from cerebellum. Together, these results demonstrate region specific, age-related, alterations in mitochondrial responses to Ca 2+.

Original languageEnglish
Pages (from-to)401-406
Number of pages6
JournalJournal of Bioenergetics and Biomembranes
Volume36
Issue number4 SPEC.ISS.
DOIs
StatePublished - Aug 2004

Bibliographical note

Funding Information:
This work was supported by a grant from the Alzheimer’s Association (to J. W. G..), and by the National Institutes of Health, U.S. Public Health Service grants NS048191 (to P.G.S.), and AG10836 (to J.W.G.). M.R.B. is a predoctoral trainee on a National Institutes of Health Training Grant AG00264.

Keywords

  • Mitochondria
  • aging
  • calcium
  • mitochondrial permeability transition
  • rat
  • reactive oxygen species

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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