Metabolic alterations induced by sucrose intake and Alzheimer's disease promote similar brain mitochondrial abnormalities

Cristina Carvalho, Susana Cardoso, Sónia C Correia, Renato X Santos, Maria S Santos, Inês Baldeiras, Catarina R Oliveira, Paula I Moreira

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Evidence shows that diabetes increases the risk of developing Alzheimer's disease (AD). Many efforts have been done to elucidate the mechanisms linking diabetes and AD. To demonstrate that mitochondria may represent a functional link between both pathologies, we compared the effects of AD and sucrose-induced metabolic alterations on mouse brain mitochondrial bioenergetics and oxidative status. For this purpose, brain mitochondria were isolated from wild-type (WT), triple transgenic AD (3xTg-AD), and WT mice fed 20% sucrose-sweetened water for 7 months. Polarography, spectrophotometry, fluorimetry, high-performance liquid chromatography, and electron microscopy were used to evaluate mitochondrial function, oxidative status, and ultrastructure. Western blotting was performed to determine the AD pathogenic protein levels. Sucrose intake caused metabolic alterations like those found in type 2 diabetes. Mitochondria from 3xTg-AD and sucrose-treated WT mice presented a similar impairment of the respiratory chain and phosphorylation system, decreased capacity to accumulate calcium, ultrastructural abnormalities, and oxidative imbalance. Interestingly, sucrose-treated WT mice presented a significant increase in amyloid β protein levels, a hallmark of AD. These results show that in mice, the metabolic alterations associated to diabetes contribute to the development of AD-like pathologic features.

Original languageEnglish
Pages (from-to)1234-1242
Number of pages9
JournalDiabetes
Volume61
Issue number5
Early online date16 Mar 2012
DOIs
Publication statusPublished - May 2012

Keywords

  • Alzheimer Disease/genetics
  • Animals
  • Antioxidants
  • Brain/cytology
  • Calcium/metabolism
  • Diabetes Complications/genetics
  • Diabetes Mellitus, Type 2/complications
  • Electron Transport
  • Energy Metabolism
  • Gene Expression Regulation
  • Glutathione/metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Mitochondria/drug effects
  • Mitochondrial Membrane Transport Proteins/drug effects
  • Oxidative Stress
  • Phosphorylation
  • Random Allocation
  • Sucrose/adverse effects
  • Vitamin E/metabolism

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  • Cite this

    Carvalho, C., Cardoso, S., Correia, S. C., Santos, R. X., Santos, M. S., Baldeiras, I., Oliveira, C. R., & Moreira, P. I. (2012). Metabolic alterations induced by sucrose intake and Alzheimer's disease promote similar brain mitochondrial abnormalities. Diabetes, 61(5), 1234-1242. https://doi.org/10.2337/db11-1186