Decreased mitochondrial bioenergetics and calcium buffering capacity in the basal ganglia correlates with motor deficits in anonhuman primate model of aging

Jignesh D. Pandya, Richard Grondin, Heather M. Yonutas, Hamed Haghnazar, Don M. Gash, Zhiming Zhang, Patrick G. Sullivan

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Altered mitochondrial function in the basal ganglia has been hypothesized to underlie cellular senescence and promote age-related motor decline. We tested this hypothesis in a nonhuman primate model of human aging. Six young (6-8 years old) and 6 aged (20-25 years old) female Rhesus monkeys (Macaca mulatta) were behaviorally characterized from standardized video records. Additionally, we measured mitochondrial bioenergetics along with calcium buffering capacity in the substantia nigra and putamen (PUT) from both age groups. Our results demonstrate that the aged animals had significantly reduced locomotor activity and movement speed compared with younger animals. Moreover, aged monkeys had significantly reduced ATP synthesis capacity (in substantia nigra and PUT), reduced pyruvate dehydrogenase activity (in PUT), and reduced calcium buffering capacity (in PUT) compared with younger animals. Furthermore, this age-related decline in mitochondrial function in the basal ganglia correlated with decline in motor function. Overall, our results suggest that drug therapies designed to enhance altered mitochondrial function may help improve motor deficits in the elderly.

Original languageEnglish
Pages (from-to)1903-1913
Number of pages11
JournalNeurobiology of Aging
Volume36
Issue number5
DOIs
StatePublished - 2015

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health grant NS 48191 and Kentucky Spinal Cord and Head Injury Research Trust (KSCHIRT) chair endowment funds (to PGS).

Publisher Copyright:
© 2015 Elsevier Inc.

Keywords

  • Aging
  • Alzheimer's disease
  • Brain
  • Calcium buffering
  • Mitochondria
  • Mitochondrial permeability transition pore
  • Parkinson's disease
  • Parkinsonism
  • Pyruvate dehydrogenase complex enzyme activity
  • Respiration
  • Rhesus monkeys

ASJC Scopus subject areas

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

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