β-Amyloid fragment 25-35 causes mitochondrial dysfunction in primary cortical neurons

C. S. Casley, J. M. Land, M. A. Sharpe, J. B. Clark, M. R. Duchen, L. Canevari

Research output: Contribution to journalArticle

175 Scopus citations

Abstract

β-Amyloid deposition and compromised energy metabolism both occur in vulnerable brain regions in Alzheimer's disease. It is not known whether β-amyloid is the cause of impairment of energy metabolism, nor whether impaired energy metabolism is specific to neurons. Our results, using primary neuronal cultures, show that 24-h incubation with Aβ25-35 caused a generalized decrease in the specific activity of mitochondrial enzymes per milligram of cellular protein, induced mitochondrial swelling, and decreased total mitochondrial number. Incubation with Aβ25-35 decreased ATP concentration to 58% of control in neurons and 71% of control in astrocytes. Levels of reduced glutathione were also lowered by Aβ25-35 in both neurons (from 5.1 to 2.9 nmol/mg protein) and astrocytes (from 25.2 to 14.9 nmol/mg protein). We conclude that 24-h treatment with extracellular Aβ25-35 causes mitochondrial dysfunction in both astrocytes and neurons, the latter being more seriously affected. In astrocytes mitochondrial impairment was confined to complex I inhibition, whereas in neurons a generalized loss of mitochondria was seen.

Original languageEnglish (US)
Pages (from-to)258-267
Number of pages10
JournalNeurobiology of Disease
Volume10
Issue number3
DOIs
StatePublished - 2002

Keywords

  • 3-amyloid
  • Alzheimer's disease
  • Astrocyte
  • Mitochondria
  • Neuron

ASJC Scopus subject areas

  • Neurology

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